We have studied gender differences in the direct and indirect sympathomimetic cardiovascular effects of the stimulant cathinone (from Khat) (and for comparison methylenedioxymethamphetamine [MDMA]) and the archetypal indirect sympathomimetic agent tyramine, employing male and female Wistar rats.
Animals were sympathectomized by treatment with 6-hydroxydopamine or treated with vehicle.
In male and female vehicle-treated pentobarbitone-anaesthetized rats, all three agonists (0.001–1 mg/kg) produced significant tachycardia, tyramine produced large pressor, and in high doses small depressor responses, MDMA produced small pressor responses, and cathinone produced only minor pressor effects.
In sympathectomized rats, pressor responses, even those to tyramine, were virtually abolished, and depressor responses to tyramine were abolished.
In vehicle-treated rats, the tachycardia to tyramine, but not the tachycardia to cathinone or MDMA, was significantly greater in male than female rats. This may suggest that the mechanism of the tachycardia to tyramine differs from those of the stimulants cathinone and MDMA. Following sympathectomy, there were no differences between male and female rats in the tachycardia to any agent.
Hence, there were gender differences in the tachycardia response for tyramine, but no gender differences in the cardiovascular responses to the widely used recreational stimulants cathinone and MDMA. Cardiac stimulant actions of cathinone and MDMA were similar in male and female rats.
{"title":"Investigation of gender differences in the cardiovascular actions of direct and indirect sympathomimetic stimulants including cathinone in the anaesthetized rat","authors":"H. A. Alsufyani, J. R. Docherty","doi":"10.1111/aap.12043","DOIUrl":"10.1111/aap.12043","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>We have studied gender differences in the direct and indirect sympathomimetic cardiovascular effects of the stimulant cathinone (from Khat) (and for comparison methylenedioxymethamphetamine [MDMA]) and the archetypal indirect sympathomimetic agent tyramine, employing male and female Wistar rats.</li>\u0000 \u0000 \u0000 <li>Animals were sympathectomized by treatment with 6-hydroxydopamine or treated with vehicle.</li>\u0000 \u0000 \u0000 <li>In male and female vehicle-treated pentobarbitone-anaesthetized rats, all three agonists (0.001–1 mg/kg) produced significant tachycardia, tyramine produced large pressor, and in high doses small depressor responses, MDMA produced small pressor responses, and cathinone produced only minor pressor effects.</li>\u0000 \u0000 \u0000 <li>In sympathectomized rats, pressor responses, even those to tyramine, were virtually abolished, and depressor responses to tyramine were abolished.</li>\u0000 \u0000 \u0000 <li>In vehicle-treated rats, the tachycardia to tyramine, but not the tachycardia to cathinone or MDMA, was significantly greater in male than female rats. This may suggest that the mechanism of the tachycardia to tyramine differs from those of the stimulants cathinone and MDMA. Following sympathectomy, there were no differences between male and female rats in the tachycardia to any agent.</li>\u0000 \u0000 \u0000 <li>Hence, there were gender differences in the tachycardia response for tyramine, but no gender differences in the cardiovascular responses to the widely used recreational stimulants cathinone and MDMA. Cardiac stimulant actions of cathinone and MDMA were similar in male and female rats.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34315019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dry stigmas of the Crocus sativus L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart.
This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat.
Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated.
The heart rate decreased and RR interval increased in Saf200 and Amio groups (P<.05 vs other groups). Square root of the mean squared differences of successive RR intervals enhanced in all treated groups, however, was only significant in Amio group (P<.05). The SD1/SD2 ratio was higher in Saf200 and Amio groups. Both low-frequency (LF) and high-frequency (HF) parameters were higher, and the LF/HF ratio was non-significantly lower in treated groups.
The findings suggest that saffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat.
{"title":"The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone","authors":"Siyavash Joukar, Mohammad-Moein Dehesh","doi":"10.1111/aap.12040","DOIUrl":"10.1111/aap.12040","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>Dry stigmas of the <i>Crocus sativus</i> L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart.</li>\u0000 \u0000 \u0000 <li>This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat.</li>\u0000 \u0000 \u0000 <li>Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated.</li>\u0000 \u0000 \u0000 <li>The heart rate decreased and RR interval increased in Saf200 and Amio groups (<i>P</i><.05 vs other groups). Square root of the mean squared differences of successive RR intervals enhanced in all treated groups, however, was only significant in Amio group (<i>P</i><.05). The SD1/SD2 ratio was higher in Saf200 and Amio groups. Both low-frequency (LF) and high-frequency (HF) parameters were higher, and the LF/HF ratio was non-significantly lower in treated groups.</li>\u0000 \u0000 \u0000 <li>The findings suggest that saffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34599673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is with great pleasure and no little trepidation that I assume my role as the fourth editor of Autonomic & Autacoid Pharmacology. It is a privilege to follow in the footsteps of Michael Day, Kenneth Broadley and William Ford. I hope that I will prove to be a worthy successor to these great custodians of the journal. I look forward to receiving submissions of manuscripts describing original work and reviews of the literature. Coincident with my commencement of editorial responsibilities is the introduction by the publishers, John Wiley & Sons, of a new page design. I hope that readers will agree with me that the more modern formatting suits the journal very well. Contributors should please note that the new style necessitates some changes in the formatting of manuscripts for submission. The journal started life in 1980 as The Journal of Autonomic Pharmacology. Michael Day’s inaugural editorial makes fascinating reading as a brief overview of the development of autonomic pharmacology as a discipline.1 Day was keen to encourage the submission of articles designated as ‘Historical Perspectives’. He explained: ‘These will be concerned with the historical development of autonomic pharmacology and may take the form of a description of a particular discovery of of the work of an individual or group. The historical aspects of a subject are more than merely of curiosity value, since they form the intellectual base on which the subject continues to grow and often contain valuable clues and hints which did not fit the contemporary framework of knowledge’. This is clearly as important today, as it was in 1980, and I would be delighted to receive submissions of this type. Authors of ‘Historical Perspectives’ will find themselves in very good company. The first publication of this type in this journal was written by no less than Raymond Ahlquist, and readers will nor be surprised to learn that it discussed the classification of adrenoceptors.2 The current title, Autonomic & Autacoid Pharmacology, was adopted in 2002, by the journal’s second editor, Ken Broadley. This was not a conscious decision to change direction, but a ‘formalizing of the natural evolution of the scope of the journal’;3 indeed, the most highly cited article published in the journal (693 citations according to Google Scholar) is the paper ‘Tachykinin receptors and Tachykinin receptor antagonists’ by Maggi et al.4, published in 1993, which illustrates that the scope of the journal had moved beyond strictly ‘autonomic’ pharmacology sometime previously. Nevertheless, in contrast to ‘autonomic pharmacology’ which can be defined and limited reasonably easily, the definition of ‘autacoid’ is perhaps harder to pin down. It is possible that authors may have been reluctant to submit their work, not knowing whether the subjects of their papers could be considered ‘autacoids’. I am very pleased therefore that Jan Keppel Hesselink has contributed an article entitled ‘The terms ‘autacoid,’ ‘hormone’ an
{"title":"Autonomic & Autacoid Pharmacology: past, present and future","authors":"Peter E. Penson","doi":"10.1111/aap.12039","DOIUrl":"10.1111/aap.12039","url":null,"abstract":"It is with great pleasure and no little trepidation that I assume my role as the fourth editor of Autonomic & Autacoid Pharmacology. It is a privilege to follow in the footsteps of Michael Day, Kenneth Broadley and William Ford. I hope that I will prove to be a worthy successor to these great custodians of the journal. I look forward to receiving submissions of manuscripts describing original work and reviews of the literature. Coincident with my commencement of editorial responsibilities is the introduction by the publishers, John Wiley & Sons, of a new page design. I hope that readers will agree with me that the more modern formatting suits the journal very well. Contributors should please note that the new style necessitates some changes in the formatting of manuscripts for submission. The journal started life in 1980 as The Journal of Autonomic Pharmacology. Michael Day’s inaugural editorial makes fascinating reading as a brief overview of the development of autonomic pharmacology as a discipline.1 Day was keen to encourage the submission of articles designated as ‘Historical Perspectives’. He explained: ‘These will be concerned with the historical development of autonomic pharmacology and may take the form of a description of a particular discovery of of the work of an individual or group. The historical aspects of a subject are more than merely of curiosity value, since they form the intellectual base on which the subject continues to grow and often contain valuable clues and hints which did not fit the contemporary framework of knowledge’. This is clearly as important today, as it was in 1980, and I would be delighted to receive submissions of this type. Authors of ‘Historical Perspectives’ will find themselves in very good company. The first publication of this type in this journal was written by no less than Raymond Ahlquist, and readers will nor be surprised to learn that it discussed the classification of adrenoceptors.2 The current title, Autonomic & Autacoid Pharmacology, was adopted in 2002, by the journal’s second editor, Ken Broadley. This was not a conscious decision to change direction, but a ‘formalizing of the natural evolution of the scope of the journal’;3 indeed, the most highly cited article published in the journal (693 citations according to Google Scholar) is the paper ‘Tachykinin receptors and Tachykinin receptor antagonists’ by Maggi et al.4, published in 1993, which illustrates that the scope of the journal had moved beyond strictly ‘autonomic’ pharmacology sometime previously. Nevertheless, in contrast to ‘autonomic pharmacology’ which can be defined and limited reasonably easily, the definition of ‘autacoid’ is perhaps harder to pin down. It is possible that authors may have been reluctant to submit their work, not knowing whether the subjects of their papers could be considered ‘autacoids’. I am very pleased therefore that Jan Keppel Hesselink has contributed an article entitled ‘The terms ‘autacoid,’ ‘hormone’ an","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34599672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We wanted to assess whether β-adrenoceptors mediate proliferation in the normal and malignant urothelial cell lines UROtsa and T24, respectively.
Urothelial cells were cultured for 24 h in the presence of the β-adrenoceptor agonists isoprenaline (β1/2/3), dobutamine (β1), salbutamol (β2), BRL 37344 (β3), CGP 12177 (a partial β-agonist) or β-adrenoceptor antagonists (metoprolol; β1, propranolol; β1/2). Phosphorylation of kinases was screened with a Human Phospho-Kinase Array Kit (R&D systems). Intracellular pathways activated by proliferation of urothelial cells were characterized by incubating cells with the MEK1/2 inhibitor PD 98,059, the p38 kinase inhibitor losmapimod or with the Akt 1/2 kinase inhibitor. Proliferation was assessed with the MTT proliferation assay (ATCC). Western blot and immunocytochemistry were used for detection of the β1-adrenoceptor.
Isoprenaline and dobutamine induced proliferation, while salbutamol and BRL 37344 did not. Dobutamine-induced proliferation was not affected by metoprolol or propranolol but was instead antagonized by CGP 12177 in T24 but not in UROtsa. In response to stimulation with dobutamine, Akt1/2/3 was phosphorylated in UROtsa, while ERK1/2 and p38 were phosphorylated in T24. MEK1/2 inhibition blocked basal and dobutamine-induced proliferation in T24 but only basal proliferation in UROtsa. Losmapimod slightly inhibited basal proliferation in T24 but not dobutamine-induced proliferation. Akt 1/2 inhibitor blocked basal and dobutamine-induced proliferation in UROtsa. Immunocytochemistry and Western blot revealed expression of β1-adrenoceptors in both urothelial cell lines.
The present data show that the urothelium expresses atypical β1-adrenoceptors that activate intracellular kinases inducing urothelial proliferation.
{"title":"Proliferation of the human urothelium is induced by atypical β1-adrenoceptors","authors":"M. Winder, C. Wasén, P. Aronsson, D. Giglio","doi":"10.1111/aap.12036","DOIUrl":"10.1111/aap.12036","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>We wanted to assess whether β-adrenoceptors mediate proliferation in the normal and malignant urothelial cell lines UROtsa and T24, respectively.</li>\u0000 \u0000 \u0000 <li>Urothelial cells were cultured for 24 h in the presence of the β-adrenoceptor agonists isoprenaline (β<sub>1/2/3</sub>), dobutamine (β<sub>1</sub>), salbutamol (β<sub>2</sub>), BRL 37344 (β<sub>3</sub>), CGP 12177 (a partial β-agonist) or β-adrenoceptor antagonists (metoprolol; β<sub>1</sub>, propranolol; β<sub>1/2</sub>). Phosphorylation of kinases was screened with a Human Phospho-Kinase Array Kit (R&D systems). Intracellular pathways activated by proliferation of urothelial cells were characterized by incubating cells with the MEK1/2 inhibitor PD 98,059, the p38 kinase inhibitor losmapimod or with the Akt 1/2 kinase inhibitor. Proliferation was assessed with the MTT proliferation assay (ATCC). Western blot and immunocytochemistry were used for detection of the β<sub>1</sub>-adrenoceptor.</li>\u0000 \u0000 \u0000 <li>Isoprenaline and dobutamine induced proliferation, while salbutamol and BRL 37344 did not. Dobutamine-induced proliferation was not affected by metoprolol or propranolol but was instead antagonized by CGP 12177 in T24 but not in UROtsa. In response to stimulation with dobutamine, Akt1/2/3 was phosphorylated in UROtsa, while ERK1/2 and p38 were phosphorylated in T24. MEK1/2 inhibition blocked basal and dobutamine-induced proliferation in T24 but only basal proliferation in UROtsa. Losmapimod slightly inhibited basal proliferation in T24 but not dobutamine-induced proliferation. Akt 1/2 inhibitor blocked basal and dobutamine-induced proliferation in UROtsa. Immunocytochemistry and Western blot revealed expression of β<sub>1</sub>-adrenoceptors in both urothelial cell lines.</li>\u0000 \u0000 \u0000 <li>The present data show that the urothelium expresses atypical β1-adrenoceptors that activate intracellular kinases inducing urothelial proliferation.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77022210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. A. Gallardo-Ortíz, S. N. Rodríguez-Hernández, J. J. López-Guerrero, L. Del Valle-Mondragón, P. López-Sánchez, R. M. Touyz, R. Villalobos-Molina
The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1-adrenoceptors (α1-ARs) expression was explored.
Alzet® minipumps filled with Ang II (200 ng kg−1 min−1) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1R antagonist, or with BMY 7378, a selective α1D-AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses.
Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups.
Angiotensin II decreased α1D-ARs without modifying the other α1-ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1Rs and α1D-ARs. Angiotensin II-induced α1D-AR-mediated vascular remodeling occurs independently of hypertension.
Findings identify a α1D-AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation.
{"title":"Role of α1D-adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension","authors":"I. A. Gallardo-Ortíz, S. N. Rodríguez-Hernández, J. J. López-Guerrero, L. Del Valle-Mondragón, P. López-Sánchez, R. M. Touyz, R. Villalobos-Molina","doi":"10.1111/aap.12035","DOIUrl":"10.1111/aap.12035","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>The <i>in vivo</i> effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α<sub>1</sub>-adrenoceptors (α<sub>1</sub>-ARs) expression was explored.</li>\u0000 \u0000 \u0000 <li>Alzet<sup>®</sup> minipumps filled with Ang II (200 ng kg<sup>−1</sup> min<sup>−1</sup>) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT<sub>1</sub>R antagonist, or with BMY 7378, a selective α<sub>1D</sub>-AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses.</li>\u0000 \u0000 \u0000 <li>Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 m<span>m</span>. Responses in tail arteries were not significantly different among the different groups.</li>\u0000 \u0000 \u0000 <li>Angiotensin II decreased α<sub>1D</sub>-ARs without modifying the other α<sub>1</sub>-ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT<sub>1</sub>Rs and α<sub>1D</sub>-ARs. Angiotensin II-induced α<sub>1D</sub>-AR-mediated vascular remodeling occurs independently of hypertension.</li>\u0000 \u0000 \u0000 <li>Findings identify a α<sub>1D</sub>-AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91021081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The increase of knowledge in a particular field (endocrinology) can be understood if one follows how certain key concepts were constructed and transformed over time. To explore such construction and transformation (shifts in meaning), we studied the use of the concepts ‘autacoid’ and ‘chalone’ in a period of one century (1916–2016), since the introduction of these concepts by the British professor of physiology Sir Sharpey-Schäfer.
We could identify that the use of ‘autacoid’ shifted from a very broad category encompassing both stimulating and inhibiting hormones, in the period 1916–1960, to a much more specific use of the term for locally produced bioactive molecules, from the 1960s onwards.
Histamine was the first compound seen as an ‘autacoid’, followed by prostaglandins, ATP, ADP and bradykinin, and from 1993 onwards, compounds such as ‘palmitoylethanolamide’ were also classified as ‘autacoids’. For ‘chalone’, a comparable shift was noticed around the 1960s, when the concept suddenly changed from the category of inhibiting hormones into a substance that is produced within a tissue, inhibiting mitosis of the cells of that tissue. For both concept shifts, we could not find any argument.
Around 1980, authors started to relate autacoids to various promising indications in the field of inflammation and immune modulation. The Nobel laureate Rita Levi-Montalcini gave an extra dimension to the concept autacoid in 1993, and introduced a new class of compounds modulating mast cells, the ALIAmides (from Autacoid Local Inflammation Antagonist), of which palmitoylethanolamide was the prototype. Our exploration demonstrates that biomedical concepts can be constructed and defined differently as time goes by, while concept transformations seem to emerge without arguments.
一个特定领域(内分泌学)的知识增长可以理解，如果一个人遵循某些关键概念是如何随着时间的推移而构建和转变的。为了探索这种结构和转换(意义的转变)，我们研究了一个世纪(1916-2016)期间“autotacoid”和“chalone”概念的使用，因为这些概念是由英国生理学教授Sir Sharpey-Schäfer引入的。我们可以确定，在1916-1960年期间，“自体类”的使用从一个非常广泛的类别，包括刺激和抑制激素，转变为更具体的术语，用于本地生产的生物活性分子，从20世纪60年代开始。组胺是第一个被视为“类自身”的化合物，其次是前列腺素、ATP、ADP和缓激素，从1993年起，“棕榈酰乙醇酰胺”等化合物也被归类为“类自身”。“chalone”在20世纪60年代前后出现了类似的变化，当时这个概念突然从抑制激素的范畴转变为组织内产生的一种物质，可以抑制该组织细胞的有丝分裂。对于这两种观念的转变，我们都找不到任何论据。1980年前后，作者开始将类自身素与炎症和免疫调节领域的各种有希望的适应症联系起来。1993年，诺贝尔奖得主丽塔·列维-蒙塔奇尼(Rita levy - montalcini)给自体类细胞的概念增加了一个维度，并介绍了一类调节肥大细胞的新化合物ALIAmides(来自自体类局部炎症拮抗剂)，其中棕榈酰乙醇酰胺是其原型。我们的探索表明，随着时间的推移，生物医学概念可以被不同地构建和定义，而概念转换似乎没有争论。
{"title":"The terms ‘autacoid’, ‘hormone’ and ‘chalone’ and how they have shifted with time","authors":"J. M. Keppel Hesselink","doi":"10.1111/aap.12037","DOIUrl":"10.1111/aap.12037","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>The increase of knowledge in a particular field (endocrinology) can be understood if one follows how certain key concepts were constructed and transformed over time. To explore such construction and transformation (shifts in meaning), we studied the use of the concepts ‘autacoid’ and ‘chalone’ in a period of one century (1916–2016), since the introduction of these concepts by the British professor of physiology Sir Sharpey-Schäfer.</li>\u0000 \u0000 \u0000 <li>We could identify that the use of ‘autacoid’ shifted from a very broad category encompassing both stimulating and inhibiting hormones, in the period 1916–1960, to a much more specific use of the term for locally produced bioactive molecules, from the 1960s onwards.</li>\u0000 \u0000 \u0000 <li>Histamine was the first compound seen as an ‘autacoid’, followed by prostaglandins, ATP, ADP and bradykinin, and from 1993 onwards, compounds such as ‘palmitoylethanolamide’ were also classified as ‘autacoids’. For ‘chalone’, a comparable shift was noticed around the 1960s, when the concept suddenly changed from the category of inhibiting hormones into a substance that is produced within a tissue, inhibiting mitosis of the cells of that tissue. For both concept shifts, we could not find any argument.</li>\u0000 \u0000 \u0000 <li>Around 1980, authors started to relate autacoids to various promising indications in the field of inflammation and immune modulation. The Nobel laureate Rita Levi-Montalcini gave an extra dimension to the concept autacoid in 1993, and introduced a new class of compounds modulating mast cells, the ALIAmides (from Autacoid Local Inflammation Antagonist), of which palmitoylethanolamide was the prototype. Our exploration demonstrates that biomedical concepts can be constructed and defined differently as time goes by, while concept transformations seem to emerge without arguments.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83811842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. L. Kumar, B. Guruprasad, P. Chaudhary, S. M. A. Fatmi, R. S. B. Oliveira, M. V. Ramos
The non-dialysable proteins present in the latex of plant Calotropis procera possess anti-inflammatory and analgesic properties.
The aim of this study was to evaluate the effect of latex proteins (LP) on the level of inflammatory mediators, oxidative stress markers and tissue histology in the rat model of carrageenan-induced acute inflammation. This study also aimed at evaluating the anti-inflammatory efficacy of LP against different mediators and comparing it with their respective antagonists.
Paw inflammation was induced by subplantar injection of carrageenan, and the effect of LP was evaluated on oedema volume, level of TNF-α, PGE2, myeloperoxidase, nitric oxide, reduced glutathione, thiobarbituric acid-reactive substances and tissue histology at the time of peak inflammation.
Paw inflammation was also induced by histamine, serotonin, bradykinin and PGE2, and the inhibitory effect of LP against these mediators was compared with their respective antagonists at the time of peak effect.
Treatment with LP produced a dose-dependent inhibition of oedema formation, and its anti-inflammatory effect against carrageenan-induced paw inflammation was accompanied by reduction in the levels of inflammatory mediators, oxidative stress markers and normalization of tissue architecture.
LP also produced a dose-dependent inhibition of oedema formation induced by different inflammatory mediators, and its efficacy was comparable to their respective antagonists and more pronounced than that of diclofenac.
Thus, our study shows that LP has a potential to be used for the treatment of various inflammatory conditions where the role of these mediators is well established.
{"title":"Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat","authors":"V. L. Kumar, B. Guruprasad, P. Chaudhary, S. M. A. Fatmi, R. S. B. Oliveira, M. V. Ramos","doi":"10.1111/aap.12022","DOIUrl":"10.1111/aap.12022","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>The non-dialysable proteins present in the latex of plant <i>Calotropis procera</i> possess anti-inflammatory and analgesic properties.</li>\u0000 \u0000 \u0000 <li>The aim of this study was to evaluate the effect of latex proteins (LP) on the level of inflammatory mediators, oxidative stress markers and tissue histology in the rat model of carrageenan-induced acute inflammation. This study also aimed at evaluating the anti-inflammatory efficacy of LP against different mediators and comparing it with their respective antagonists.</li>\u0000 \u0000 \u0000 <li>Paw inflammation was induced by subplantar injection of carrageenan, and the effect of LP was evaluated on oedema volume, level of TNF-α, PGE<sub>2</sub>, myeloperoxidase, nitric oxide, reduced glutathione, thiobarbituric acid-reactive substances and tissue histology at the time of peak inflammation.</li>\u0000 \u0000 \u0000 <li>Paw inflammation was also induced by histamine, serotonin, bradykinin and PGE<sub>2</sub>, and the inhibitory effect of LP against these mediators was compared with their respective antagonists at the time of peak effect.</li>\u0000 \u0000 \u0000 <li>Treatment with LP produced a dose-dependent inhibition of oedema formation, and its anti-inflammatory effect against carrageenan-induced paw inflammation was accompanied by reduction in the levels of inflammatory mediators, oxidative stress markers and normalization of tissue architecture.</li>\u0000 \u0000 \u0000 <li>LP also produced a dose-dependent inhibition of oedema formation induced by different inflammatory mediators, and its efficacy was comparable to their respective antagonists and more pronounced than that of diclofenac.</li>\u0000 \u0000 \u0000 <li>Thus, our study shows that LP has a potential to be used for the treatment of various inflammatory conditions where the role of these mediators is well established.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33225613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study was designed to evaluate the effects of oral administration of Echinacea hydroethanolic extract on the dog's immune system.
The study was performed on 14 dogs that were referred to the veterinary clinic. These dogs were randomly allocated to two equal treatment groups. The first group received 1 ml of 5% Echinacea hydroethanolic extract two times a day for 2 months, and the second group received a placebo (water). To do haematology and immunology tests, the dogs were bled on days 0, 30 and 60. Blood tests, including packed cell volume (PCV), haemoglobin (Hb), red blood cell count (RBC), white blood cell count (WBC), counting neutrophils (Nut), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), basophils (Baso) and B cell, were performed. Furthermore, safety factor IgM and per cent of phagocytosis and phagocyte were measured from the blood sample.
The results showed that in the group which received Echinacea PCV, Hb, RBC count, WBC count, Lym, Nut, the per cent of phagocytosis and IgM significantly increased (P < 0.05). Moreover, positive effects of Echinacea plant on the immune system were observed. There was a significant change in HTC, RBC, Hb over time in the group that received Echinacea and the per cent of phagocytosis and IgM (P < 0.05).
The study establishes that these extracts might have appreciable immunostimulatory activity. However, further studies are required to confirm these findings.
{"title":"Evaluating the effect of oral administration of Echinacea hydroethanolic extract on the immune system in dog","authors":"S. Torkan, F. Khamesipour, S. Katsande","doi":"10.1111/aap.12024","DOIUrl":"10.1111/aap.12024","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>This study was designed to evaluate the effects of oral administration of <i>Echinacea</i> hydroethanolic extract on the dog's immune system.</li>\u0000 \u0000 \u0000 <li>The study was performed on 14 dogs that were referred to the veterinary clinic. These dogs were randomly allocated to two equal treatment groups. The first group received 1 ml of 5% <i>Echinacea</i> hydroethanolic extract two times a day for 2 months, and the second group received a placebo (water). To do haematology and immunology tests, the dogs were bled on days 0, 30 and 60. Blood tests, including packed cell volume (PCV), haemoglobin (Hb), red blood cell count (RBC), white blood cell count (WBC), counting neutrophils (Nut), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), basophils (Baso) and B cell, were performed. Furthermore, safety factor IgM and per cent of phagocytosis and phagocyte were measured from the blood sample.</li>\u0000 \u0000 \u0000 <li>The results showed that in the group which received <i>Echinacea </i>PCV, Hb, RBC count, WBC count, Lym, Nut, the per cent of phagocytosis and IgM significantly increased (<i>P</i> < 0.05). Moreover, positive effects of <i>Echinacea</i> plant on the immune system were observed. There was a significant change in HTC, RBC, Hb over time in the group that received <i>Echinacea</i> and the per cent of phagocytosis and IgM (<i>P</i> < 0.05).</li>\u0000 \u0000 \u0000 <li>The study establishes that these extracts might have appreciable immunostimulatory activity. However, further studies are required to confirm these findings.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33061913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams
Alpha1-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L-adrenoceptor) is involved in mediating contractions of this tissue.
The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [3H]tamsulosin binding experiments to identify the α1-adrenoceptor subtype population present in the human vas deferens.
The α1A-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D-adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A- and α1D-adrenoceptor selective) had a high affinity (pKd = 9.9).
[3H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [3H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively).
These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1-adrenoceptors which have the pharmacological properties of the putative α1L-adrenoceptor, the same functional receptor previously identified in the human prostate.
{"title":"Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens","authors":"B. J. Davis, M. Wiener, C. R. Chapple, D. J. Sellers, R. Chess-Williams","doi":"10.1111/aap.12023","DOIUrl":"10.1111/aap.12023","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>Alpha<sub>1</sub>-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α<sub>1A</sub>-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α<sub>1L</sub>-adrenoceptor) is involved in mediating contractions of this tissue.</li>\u0000 \u0000 \u0000 <li>The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [<sup>3</sup>H]tamsulosin binding experiments to identify the α<sub>1</sub>-adrenoceptor subtype population present in the human vas deferens.</li>\u0000 \u0000 \u0000 <li>The α<sub>1A</sub>-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pK<sub>d</sub> = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α<sub>1D</sub>-adrenoceptor selective) gave a low affinity estimate (pK<sub>d</sub> = 6.7), whilst tamsulosin (α<sub>1A</sub>- and α<sub>1D</sub>-adrenoceptor selective) had a high affinity (pK<sub>d</sub> = 9.9).</li>\u0000 \u0000 \u0000 <li>[<sup>3</sup>H]Tamsulosin bound to human vas deferens membranes with a high affinity (pK<sub>d</sub> = 10.0). Prazosin, RS17053 and BMY7378 competed with [<sup>3</sup>H]tamsulosin with low affinities for a single population of binding sites (pK<sub>d</sub> values of 8.5, 7.2 and 6.3, respectively).</li>\u0000 \u0000 \u0000 <li>These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α<sub>1</sub>-adrenoceptors which have the pharmacological properties of the putative α<sub>1L</sub>-adrenoceptor, the same functional receptor previously identified in the human prostate.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33144795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. A. Peredo, H. Lee, A. S. Donoso, V. Andrade, N. Sánchez Eluchans, A. M. Puyó
In the rat, a high-fat (HF) plus fructose (F) diet produces cardiovascular and metabolic alterations that resemble human metabolic syndrome. Prostanoids (PR), cyclo-oxygenase-derived arachidonic acid metabolites, have vasoactive properties and mediate inflammation.
The aim of this study was to analyse the effect of a HF+F diet on blood pressure (BP), metabolic parameters and mesenteric vascular bed PR production in male Sprague–Dawley rats.
Four groups were studied over 9 weeks (n = 6 each): control (C), standard diet (SD) and tap water to drink; F+SD and 10% w/v F solution to drink; HF 50% (w/w) bovine fat added to SD and tap water; and HFF, both treatments. PR were determined by HPLC.
Blood pressure was elevated in all experimental groups. Triglyceridaemia, insulinaemia and HOMA-IR were increased in the F and HF groups. HF+F animals showed elevated glycaemia, insulinaemia, HOMA-IR and triglyceridaemia. F decreased the vasodilator prostanoids PGI2 and PGE2 in the mesenteric vascular bed. Body weight was not significantly altered. In HFF, production of PGE2, PGF2alpha and TXB2 was elevated.
The increased BP in HF and HFF could be partly attributed to the imbalance in vascular PR production towards vasoconstrictors. On the other hand, this dietary modification could induce inflammation, which would explain the elevation of PGE2. In the F group, hypertension could be related to decreased vasodilator PRs.
The simultaneous administration of HF and F in the rat produces deleterious effects greater than observed when treatments are applied separately.
{"title":"A high-fat plus fructose diet produces a vascular prostanoid alterations in the rat","authors":"H. A. Peredo, H. Lee, A. S. Donoso, V. Andrade, N. Sánchez Eluchans, A. M. Puyó","doi":"10.1111/aap.12021","DOIUrl":"10.1111/aap.12021","url":null,"abstract":"<div>\u0000 \u0000 <p>\u0000 \u0000 </p><ol>\u0000 \u0000 \u0000 <li>In the rat, a high-fat (HF) plus fructose (F) diet produces cardiovascular and metabolic alterations that resemble human metabolic syndrome. Prostanoids (PR), cyclo-oxygenase-derived arachidonic acid metabolites, have vasoactive properties and mediate inflammation.</li>\u0000 \u0000 \u0000 <li>The aim of this study was to analyse the effect of a HF+F diet on blood pressure (BP), metabolic parameters and mesenteric vascular bed PR production in male Sprague–Dawley rats.</li>\u0000 \u0000 \u0000 <li>Four groups were studied over 9 weeks (<i>n</i> = 6 each): control (C), standard diet (SD) and tap water to drink; F+SD and 10% w/v F solution to drink; HF 50% (w/w) bovine fat added to SD and tap water; and HFF, both treatments. PR were determined by HPLC.</li>\u0000 \u0000 \u0000 <li>Blood pressure was elevated in all experimental groups. Triglyceridaemia, insulinaemia and HOMA-IR were increased in the F and HF groups. HF+F animals showed elevated glycaemia, insulinaemia, HOMA-IR and triglyceridaemia. F decreased the vasodilator prostanoids PGI<sub>2</sub> and PGE<sub>2</sub> in the mesenteric vascular bed. Body weight was not significantly altered. In HFF, production of PGE<sub>2</sub>, PGF<sub>2</sub>alpha and TXB<sub>2</sub> was elevated.</li>\u0000 \u0000 \u0000 <li>The increased BP in HF and HFF could be partly attributed to the imbalance in vascular PR production towards vasoconstrictors. On the other hand, this dietary modification could induce inflammation, which would explain the elevation of PGE<sub>2</sub>. In the F group, hypertension could be related to decreased vasodilator PRs.</li>\u0000 \u0000 \u0000 <li>The simultaneous administration of HF and F in the rat produces deleterious effects greater than observed when treatments are applied separately.</li>\u0000 </ol>\u0000 \u0000 </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33003258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号