We evaluated a 44-year-old female with bipolar affective disorder who presented with a 4-month history of severe stuttering and vague neurologic complaints. She had lost 200 pounds after gastric bypass surgery two years before. A childhood sexualabuse victim, she admits that she “hid” in her weight for most of her life. Neurological evaluation of this patient was negative, and speech-pathology evaluation revealed highly atypical stuttering. Gastric bypass patients with a history of psychiatric disorders and childhood sexual abuse may be particularly vulnerable to somatoform disorders. It has been widely reported that psychological complications are prevalent among the morbidly obese, although this point has been controversial (1). Glinski et al. elucidated that 70% of patients evaluated for gastric bypass surgery meet criteria for an Axis I disorder in the past or present and 36% for Axis II disorder (2). In his study, he found that the lifetime prevalence of depressive disorders alone in this population was 56%, compared with the known lifetime prevalence of depressive disorders of about 17% in the general population. Glinski noted that gastric bypass surgical candidates tend to use denial as a defense mechanism for avoiding negative emotions. In keeping with this, overeating may serve as distraction from negative emotion in these individuals. Somatization is another tendency in this particular population. Some improvement of psychosocial functioning after surgical treatment of obesity has been reported (3). Van Gemert et al. recently investigated the longterm effects of surgically induced weight loss on the psychological functioning of morbidly obese patients. They found that preoperative subjects had elevated values on negativism, somatization, and shyness scales on personality profiles; postoperatively, all these values normalized except somatization. Thus, postoperative patients still were concerned about their health and still were inclined to react to psychological stress with physical complaints.
{"title":"Psychogenic Stuttering Following a Gastric Bypass Operation: Case Report","authors":"D. Raphael, F. Schoenfeld","doi":"10.29046/JJP.020.1.002","DOIUrl":"https://doi.org/10.29046/JJP.020.1.002","url":null,"abstract":"We evaluated a 44-year-old female with bipolar affective disorder who presented with a 4-month history of severe stuttering and vague neurologic complaints. She had lost 200 pounds after gastric bypass surgery two years before. A childhood sexualabuse victim, she admits that she “hid” in her weight for most of her life. Neurological evaluation of this patient was negative, and speech-pathology evaluation revealed highly atypical stuttering. Gastric bypass patients with a history of psychiatric disorders and childhood sexual abuse may be particularly vulnerable to somatoform disorders. It has been widely reported that psychological complications are prevalent among the morbidly obese, although this point has been controversial (1). Glinski et al. elucidated that 70% of patients evaluated for gastric bypass surgery meet criteria for an Axis I disorder in the past or present and 36% for Axis II disorder (2). In his study, he found that the lifetime prevalence of depressive disorders alone in this population was 56%, compared with the known lifetime prevalence of depressive disorders of about 17% in the general population. Glinski noted that gastric bypass surgical candidates tend to use denial as a defense mechanism for avoiding negative emotions. In keeping with this, overeating may serve as distraction from negative emotion in these individuals. Somatization is another tendency in this particular population. Some improvement of psychosocial functioning after surgical treatment of obesity has been reported (3). Van Gemert et al. recently investigated the longterm effects of surgically induced weight loss on the psychological functioning of morbidly obese patients. They found that preoperative subjects had elevated values on negativism, somatization, and shyness scales on personality profiles; postoperatively, all these values normalized except somatization. Thus, postoperative patients still were concerned about their health and still were inclined to react to psychological stress with physical complaints.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"2 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75050279","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}
Despite the almost universal familiarity of mental health professionals with the Tarasoff case, many questions regarding its associated legal requirements often arise when evaluating potentially dangerous patients. The principles of the duty to warn/protect, while appearing nebulous at times, contain key concepts that the clinician must consider in the face of potential danger to third parties. This article reviews the landmark decision of the Tarasoff case and outlines its key concepts. In addition, given that state jurisdictions vary in treatment of Tarasoff-like cases, this article explores the Pennsylvania Supreme Court decision, Emerich v. Philadelphia Center for Human Development, Inc.
{"title":"The Duty to Warn/Protect Doctrine and Its Application in Pennsylvania","authors":"C. Watson","doi":"10.29046/JJP.019.1.002","DOIUrl":"https://doi.org/10.29046/JJP.019.1.002","url":null,"abstract":"Despite the almost universal familiarity of mental health professionals with the Tarasoff case, many questions regarding its associated legal requirements often arise when evaluating potentially dangerous patients. The principles of the duty to warn/protect, while appearing nebulous at times, contain key concepts that the clinician must consider in the face of potential danger to third parties. This article reviews the landmark decision of the Tarasoff case and outlines its key concepts. In addition, given that state jurisdictions vary in treatment of Tarasoff-like cases, this article explores the Pennsylvania Supreme Court decision, Emerich v. Philadelphia Center for Human Development, Inc.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"263 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75850393","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}
T. Kenning, R. Mago, Steven F Huege, K. Certa, R. Pelchat
This article presents an overview of the current knowledge and practice of ECT. It provides a brief history of the development of ECT followed by a discussion of the accepted indications for ECT in psychiatric practice, including major depression, bipolar disorder (mania and depression), and schizophrenia. Moreover, a description of the technique of performing ECT is given. Also examined are the use of ECT in medically ill patients and the risks associated with ECT. In conclusion, with the aid of advances in anesthesia and the delivery of ECT, electroconvulsive therapy is a safe and effective treatment of mood and psychotic disorders that have been resistant to other treatment modalities.
{"title":"Electroconvulsive Therapy: A Review of Its Current Status","authors":"T. Kenning, R. Mago, Steven F Huege, K. Certa, R. Pelchat","doi":"10.29046/JJP.019.1.001","DOIUrl":"https://doi.org/10.29046/JJP.019.1.001","url":null,"abstract":"This article presents an overview of the current knowledge and practice of ECT. It provides a brief history of the development of ECT followed by a discussion of the accepted indications for ECT in psychiatric practice, including major depression, bipolar disorder (mania and depression), and schizophrenia. Moreover, a description of the technique of performing ECT is given. Also examined are the use of ECT in medically ill patients and the risks associated with ECT. In conclusion, with the aid of advances in anesthesia and the delivery of ECT, electroconvulsive therapy is a safe and effective treatment of mood and psychotic disorders that have been resistant to other treatment modalities.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"54 4 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77657392","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}
{"title":"Use of Clozapine in Women of Childbearing Age: A Literature Review and Recommendations","authors":"S. Friedman, Adit Yanjee","doi":"10.29046/JJP.018.1.001","DOIUrl":"https://doi.org/10.29046/JJP.018.1.001","url":null,"abstract":"","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"50 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75523071","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 function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M) caused contractions of strips of the urinary bladder, in a concentration dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while granisetron and SB204070 antagonized the contractions induced by high concentrations of 5-HT. Atropine inhibited the contractions induced by high concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the presence of atropine, but granisetron and SB204070 did not affect the contractions under such a condition. 5-HT enhanced the electrically-stimulated (5 Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline, and the enhancement was antagonized by granisetron and SB204070. Thus, the contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5-HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a property of low affinity to 5-HT and located on the cholinergic neurons.
{"title":"5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder.","authors":"Akira Yoshida, Yasuko S-Yamashita, Muneshige Kaibara, Kohtaro Taniyama, Nobuyuki Tanaka","doi":"10.1254/jjp.89.349","DOIUrl":"https://doi.org/10.1254/jjp.89.349","url":null,"abstract":"<p><p>The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M) caused contractions of strips of the urinary bladder, in a concentration dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while granisetron and SB204070 antagonized the contractions induced by high concentrations of 5-HT. Atropine inhibited the contractions induced by high concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the presence of atropine, but granisetron and SB204070 did not affect the contractions under such a condition. 5-HT enhanced the electrically-stimulated (5 Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline, and the enhancement was antagonized by granisetron and SB204070. Thus, the contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5-HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a property of low affinity to 5-HT and located on the cholinergic neurons.</p>","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"89 4","pages":"349-55"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1254/jjp.89.349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21992964","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 newly discovered endogenous mu-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. This review focuses on differential mechanism of the motivational effects induced by EM-1 and EM-2. In the [35S]GTPgammaS binding assay, either EM-1 or EM-2 causes a concentration-dependent G-protein activation in brain membrane of normal mice, whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes obtained from the MOP-R knockout mice. These results provide direct evidence at the molecular level that both EMs act on the MOP-R as the endogenous MOP-R agonists. Based on the conditioned place preference paradigm in mice, EM-1 given intracerebroventriculally produced a dose-related place preference. This effect was abolished by pretreatment with the MOP-R antagonist beta-funaltrexamine (FNA) but not the delta-opioid receptor (DOP-R) antagonist naltrindole and the kappa-opioid receptor (KOP-R) antagonist nor-bialtorphimine (BNI). Unlike EM-1, EM-2 exhibited a place aversion. The aversive effect was inhibited by not only beta-FNA but also nor-BNI. Place aversion produced by EM-2 was also attenuated by pretreatment with an antiserum against an endogenous KOP-R ligand dynorphin A(1-17). These findings indicate that EM-1 may produce its rewarding effect via MOP-Rs. Furthermore, the aversive effect induced by EM-2 may be associated with the stimulation of the EM-1-insensitive MOP-R subtype and necessarily activate an endogenous KOPergic system in the mouse brain.
{"title":"Endomorphin-induced motivational effect: differential mechanism of endomorphin-1 and endomorphin-2.","authors":"M. Narita, S. Ozaki, Tsutomu Suzuki","doi":"10.1254/JJP.89.224","DOIUrl":"https://doi.org/10.1254/JJP.89.224","url":null,"abstract":"The newly discovered endogenous mu-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. This review focuses on differential mechanism of the motivational effects induced by EM-1 and EM-2. In the [35S]GTPgammaS binding assay, either EM-1 or EM-2 causes a concentration-dependent G-protein activation in brain membrane of normal mice, whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes obtained from the MOP-R knockout mice. These results provide direct evidence at the molecular level that both EMs act on the MOP-R as the endogenous MOP-R agonists. Based on the conditioned place preference paradigm in mice, EM-1 given intracerebroventriculally produced a dose-related place preference. This effect was abolished by pretreatment with the MOP-R antagonist beta-funaltrexamine (FNA) but not the delta-opioid receptor (DOP-R) antagonist naltrindole and the kappa-opioid receptor (KOP-R) antagonist nor-bialtorphimine (BNI). Unlike EM-1, EM-2 exhibited a place aversion. The aversive effect was inhibited by not only beta-FNA but also nor-BNI. Place aversion produced by EM-2 was also attenuated by pretreatment with an antiserum against an endogenous KOP-R ligand dynorphin A(1-17). These findings indicate that EM-1 may produce its rewarding effect via MOP-Rs. Furthermore, the aversive effect induced by EM-2 may be associated with the stimulation of the EM-1-insensitive MOP-R subtype and necessarily activate an endogenous KOPergic system in the mouse brain.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"30 1","pages":"224-8"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81637119","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}
Y. Ozaki, K. Kunimatsu, Y. Hara, I. Kato, Y. Aoki, Kenji Yamamoto, Y. Kato
To investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immunohistochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.
{"title":"An involvement of granulocyte medullasin in phenytoin-induced gingival overgrowth in rats.","authors":"Y. Ozaki, K. Kunimatsu, Y. Hara, I. Kato, Y. Aoki, Kenji Yamamoto, Y. Kato","doi":"10.1254/JJP.89.235","DOIUrl":"https://doi.org/10.1254/JJP.89.235","url":null,"abstract":"To investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immunohistochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"63 1","pages":"235-41"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86135586","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 investigated the effects of anions on different P2 receptors by measuring ATP-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded NG108-15 and PC12 cells. In NG108-15 cells, ATP at 100 microM and 1 mM induced a transient and a sustained [Ca2+]i increase, respectively. The former, but not the latter, was inhibited by U-73122, indicating that the former was via the P2Y2 receptor and the latter via the P2X7 receptor. When external Cl- was replaced by other anions, the [Ca2+]i increase mediated by the P2Y2 receptor was not changed, but that mediated by the P2X7 receptor varied in the order of aspartate- > methanesulfonate > Cl- > Br > or = I-. In PC12 cells, transient [Ca2+]i increases mediated by the P2Y2 and P2X2 receptors were not affected by various anions. These results suggest that modulation by anions is unique to the P2X7 receptor and does not occur in P2Y2 and P2X2 receptors. This may be because the mechanism of ATP binding to the P2X7 receptor may be different than that to other P2 receptors.
我们通过测量atp诱导的fura-2负载的NG108-15和PC12细胞内Ca2+浓度([Ca2+]i)的增加来研究阴离子对不同P2受体的影响。在NG108-15细胞中,100微米和1毫米ATP分别诱导瞬时和持续的[Ca2+]i升高。U-73122对前者有抑制作用,而对后者无抑制作用,说明前者是通过P2Y2受体,后者是通过P2X7受体。当外源Cl-被其他阴离子取代时,P2Y2受体介导的[Ca2+]i升高没有变化,而P2X7受体介导的[Ca2+]i升高的顺序为天冬氨酸- >甲磺酸- > Cl- > Br > or = i -。在PC12细胞中,P2Y2和P2X2受体介导的瞬时[Ca2+]i升高不受各种阴离子的影响。这些结果表明阴离子的调节是P2X7受体所特有的,而不发生在P2Y2和P2X2受体中。这可能是因为ATP与P2X7受体的结合机制可能不同于与其他P2受体的结合机制。
{"title":"Effects of anions on ATP-induced [Ca2+], increase in NG108-15 cells.","authors":"T. Watano, I. Matsuoka, K. Ogawa, J. Kimura","doi":"10.1254/JJP.89.302","DOIUrl":"https://doi.org/10.1254/JJP.89.302","url":null,"abstract":"We investigated the effects of anions on different P2 receptors by measuring ATP-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded NG108-15 and PC12 cells. In NG108-15 cells, ATP at 100 microM and 1 mM induced a transient and a sustained [Ca2+]i increase, respectively. The former, but not the latter, was inhibited by U-73122, indicating that the former was via the P2Y2 receptor and the latter via the P2X7 receptor. When external Cl- was replaced by other anions, the [Ca2+]i increase mediated by the P2Y2 receptor was not changed, but that mediated by the P2X7 receptor varied in the order of aspartate- > methanesulfonate > Cl- > Br > or = I-. In PC12 cells, transient [Ca2+]i increases mediated by the P2Y2 and P2X2 receptors were not affected by various anions. These results suggest that modulation by anions is unique to the P2X7 receptor and does not occur in P2Y2 and P2X2 receptors. This may be because the mechanism of ATP binding to the P2X7 receptor may be different than that to other P2 receptors.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"78 1","pages":"302-8"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77193013","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 investigated the effects of heavy metal ions on the ATP-induced nonselective cation current through P2X7 receptor (I(NS x P2X7)) in NG108-15 cells using the whole-cell patch-clamp technique. Cu2+ inhibited the I(NS x P2X7) most potently among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+ also inhibited the I(NS x P2X7) in concentration-dependent manners. The order of potency was Cu2+ >> Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79 microM, 1.2 microM, 3.0 microM and 4.6 microM, respectively. Fe3+ (10 and 100 microM) and Mn2+ (10 microM) did not affect the INS P2X7. A high concentration of Mn2+ (100 microM) slightly inhibited the I(NS x P2X7). When the concentration-response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the maximal response but not the EC50 value appeared to be reduced, suggesting that the inhibition is not competitive. These results suggest that under physiological and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and Co2+, may modulate P2X7 receptor channels as inhibitors.
采用全细胞膜片钳技术研究了重金属离子对NG108-15细胞中atp诱导的P2X7受体(I(NS x P2X7))非选择性阳离子电流的影响。在所研究的金属离子中,Cu2+对I(NS x P2X7)的抑制作用最强。其他金属如Ni2+, Cd2+, Zn2+和Co2+也以浓度依赖的方式抑制I(NS x P2X7)。效价顺序为Cu2+ > Ni2+ > Cd2+ > Zn2+ > Co2+, IC50值分别为16 nM、0.79微米、1.2微米、3.0微米和4.6微米。Fe3+(10和100微米)和Mn2+(10微米)对INS P2X7没有影响。高浓度Mn2+(100微米)对I(NS x P2X7)有轻微抑制作用。当3 nM和10 nM Cu2+存在时,ATP的浓度-响应曲线显示最大响应降低,但EC50值没有降低,表明抑制不是竞争性的。这些结果表明,在生理和毒理学条件下,Cu2+、Ni2+、Cd2+、Zn2+和Co2+等金属离子可能作为抑制剂调节P2X7受体通道。
{"title":"Inhibitory effects of metals on ATP-induced current through P2X7 receptor in NG108-15 cells.","authors":"T. Watano, I. Matsuoka, J. Kimura","doi":"10.1254/JJP.89.296","DOIUrl":"https://doi.org/10.1254/JJP.89.296","url":null,"abstract":"We investigated the effects of heavy metal ions on the ATP-induced nonselective cation current through P2X7 receptor (I(NS x P2X7)) in NG108-15 cells using the whole-cell patch-clamp technique. Cu2+ inhibited the I(NS x P2X7) most potently among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+ also inhibited the I(NS x P2X7) in concentration-dependent manners. The order of potency was Cu2+ >> Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79 microM, 1.2 microM, 3.0 microM and 4.6 microM, respectively. Fe3+ (10 and 100 microM) and Mn2+ (10 microM) did not affect the INS P2X7. A high concentration of Mn2+ (100 microM) slightly inhibited the I(NS x P2X7). When the concentration-response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the maximal response but not the EC50 value appeared to be reduced, suggesting that the inhibition is not competitive. These results suggest that under physiological and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and Co2+, may modulate P2X7 receptor channels as inhibitors.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"4 1","pages":"296-301"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89979115","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. Mizoguchi, L. Tseng, Tsutomu Suzuki, I. Sora, M. Narita
It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. In contrast, beta-endorphin exhibits the strongest actions among endogenous opioid peptides mainly through the MOP-R; however, it also shows the distinct pharmacological actions. Recent cloning and expression studies have indicated that MOP-Rs are seven-transmembrane domain receptors whose actions are mediated through activation of heterotrimeric guanine nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs can be measured by assessing agonist-induced stimulation of membrane binding of guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding assay.
{"title":"Differential mechanism of G-protein activation induced by endogenous mu-opioid peptides, endomorphin and beta-endorphin.","authors":"H. Mizoguchi, L. Tseng, Tsutomu Suzuki, I. Sora, M. Narita","doi":"10.1254/JJP.89.229","DOIUrl":"https://doi.org/10.1254/JJP.89.229","url":null,"abstract":"It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. In contrast, beta-endorphin exhibits the strongest actions among endogenous opioid peptides mainly through the MOP-R; however, it also shows the distinct pharmacological actions. Recent cloning and expression studies have indicated that MOP-Rs are seven-transmembrane domain receptors whose actions are mediated through activation of heterotrimeric guanine nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs can be measured by assessing agonist-induced stimulation of membrane binding of guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding assay.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"50 1","pages":"229-34"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78916981","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}