The nucleus of solitary tract (NTS) contains diverse neural circuits responsible for basic vital functions. We examined the effect of serotonin (5-HT) on hyperpolarization-activated current (I(h)) in neurons acutely isolated from caudal, medial and rostral parts of the NTS. Caudal and medial NTS neurons showed a large amplitude of I(h) compared with rostral neurons. In these neurons, perfusion with 5-HT potentiated Ih amplitude in a concentration-dependent manner. The effect of 5-HT was blocked by NAN-190, a 5-HT1A receptor antagonist. Thus, 5-HT1A receptors may regulate I(h) channel activity in caudal and medial NTS neurons.
{"title":"Hyperpolarization-activated current I(h) in nucleus of solitary tract neurons: regional difference in serotonergic modulation.","authors":"Yuki Iwahori, Y. Ikegaya, N. Matsuki","doi":"10.1254/JJP.88.459","DOIUrl":"https://doi.org/10.1254/JJP.88.459","url":null,"abstract":"The nucleus of solitary tract (NTS) contains diverse neural circuits responsible for basic vital functions. We examined the effect of serotonin (5-HT) on hyperpolarization-activated current (I(h)) in neurons acutely isolated from caudal, medial and rostral parts of the NTS. Caudal and medial NTS neurons showed a large amplitude of I(h) compared with rostral neurons. In these neurons, perfusion with 5-HT potentiated Ih amplitude in a concentration-dependent manner. The effect of 5-HT was blocked by NAN-190, a 5-HT1A receptor antagonist. Thus, 5-HT1A receptors may regulate I(h) channel activity in caudal and medial NTS neurons.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"144 1","pages":"459-62"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86753092","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}
Matlubur Rahman, S. Kimura, H. Yoneyama, H. Kosaka, T. Fukui, A. Nishiyama, Y. Abe
The present study was conducted to determine whether exogenous angiotensin II (Ang II) may increase the renal interstitial fluid concentrations of NO2/NO3 (NOx) and cyclic guanosine monophosphate (cGMP) concomitantly and which Ang II receptor subtypes may induce these changes in anesthetized rats, using a microdialysis method. Ang II (50 ng/kg per min, i.v.) significantly increased mean blood pressure (MBP), extraction rates of renal interstitial NOx from 23.9+/-1.0 to 31.2+/-1.9 pmol/min, and cGMP from 4.1+/-0.3 to 6.4+/-0.5 fmol/min, and decreased renal blood flow (RBF). The AT1-receptor antagonist CV11974 alone significantly increased RBF, but did not alter MBP, renal interstitial concentrations of NOx and cGMP. A superimposition of Ang II on CV11974 did not affect MBP and RBF, but significantly increased renal interstitial concentrations of NOx and cGMP. The AT2-receptor antagonist PD123319 alone did not change any of the parameters. However, superimposition of Ang II on PD123319 increased MBP and decreased RBF without any effects on renal interstitial concentrations of NOx and cGMP. These results suggest that Ang II stimulates NO production via the AT2-receptor in the kidney.
{"title":"Effects of angiotensin II on the renal interstitial concentrations of NO2/NO3 and cyclic GMP in anesthetized rats.","authors":"Matlubur Rahman, S. Kimura, H. Yoneyama, H. Kosaka, T. Fukui, A. Nishiyama, Y. Abe","doi":"10.1254/JJP.88.436","DOIUrl":"https://doi.org/10.1254/JJP.88.436","url":null,"abstract":"The present study was conducted to determine whether exogenous angiotensin II (Ang II) may increase the renal interstitial fluid concentrations of NO2/NO3 (NOx) and cyclic guanosine monophosphate (cGMP) concomitantly and which Ang II receptor subtypes may induce these changes in anesthetized rats, using a microdialysis method. Ang II (50 ng/kg per min, i.v.) significantly increased mean blood pressure (MBP), extraction rates of renal interstitial NOx from 23.9+/-1.0 to 31.2+/-1.9 pmol/min, and cGMP from 4.1+/-0.3 to 6.4+/-0.5 fmol/min, and decreased renal blood flow (RBF). The AT1-receptor antagonist CV11974 alone significantly increased RBF, but did not alter MBP, renal interstitial concentrations of NOx and cGMP. A superimposition of Ang II on CV11974 did not affect MBP and RBF, but significantly increased renal interstitial concentrations of NOx and cGMP. The AT2-receptor antagonist PD123319 alone did not change any of the parameters. However, superimposition of Ang II on PD123319 increased MBP and decreased RBF without any effects on renal interstitial concentrations of NOx and cGMP. These results suggest that Ang II stimulates NO production via the AT2-receptor in the kidney.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"32 1","pages":"436-41"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76895156","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}
A variety of different isoforms of voltage-sensitive Na+ channels have now been identified. The recent three-dimensional analysis of Na+ channels has unveiled a unique and unexpected structure of the Na+ channel protein. Na+ channels can be classified into two categories on the basis of their amino acid sequence, Nav1 isoforms currently comprising nine highly homologous clones and Nax that possesses structure diverging from Nav1, especially in several critical functional motifs. Although the functional role of Nav1 isoforms is primarily to form an action potential upstroke in excitable cells, recent biophysical studies indicate that some of the Nav1 isoforms can also influence subthreshold electrical activity through persistent or resurgent Na+ currents. Nav1.8 and Nav1.9 contain an amino acid sequence common to tetrodotoxin resistant Na+ channels and are localized in peripheral nociceptors. Recent patch-clamp experiments on dorsal root ganglion neurons from Nav1.8-knock-out mice unveiled an additional tetrodotoxin-resistant Na+ current. The demonstration of its dependence on Nav1.9 provides evidence for a specialized role of Nav1.9, together with Nav1.8, in pain sensation. Although Nax has not been successfully expressed in an exogenous system, recent investigations using relevant native tissues combined with gene-targeting have disclosed their unique "concentration"-sensitive but not voltage-sensitive roles. In this context, these emerging views of novel functions mediated by different types of Na+ channels are reviewed, to give a perspective for future research on the expanding family of Na+ channel clones.
{"title":"Molecular diversity of structure and function of the voltage-gated Na+ channels.","authors":"N. Ogata, Yoshiaki Ohishi","doi":"10.1254/JJP.88.365","DOIUrl":"https://doi.org/10.1254/JJP.88.365","url":null,"abstract":"A variety of different isoforms of voltage-sensitive Na+ channels have now been identified. The recent three-dimensional analysis of Na+ channels has unveiled a unique and unexpected structure of the Na+ channel protein. Na+ channels can be classified into two categories on the basis of their amino acid sequence, Nav1 isoforms currently comprising nine highly homologous clones and Nax that possesses structure diverging from Nav1, especially in several critical functional motifs. Although the functional role of Nav1 isoforms is primarily to form an action potential upstroke in excitable cells, recent biophysical studies indicate that some of the Nav1 isoforms can also influence subthreshold electrical activity through persistent or resurgent Na+ currents. Nav1.8 and Nav1.9 contain an amino acid sequence common to tetrodotoxin resistant Na+ channels and are localized in peripheral nociceptors. Recent patch-clamp experiments on dorsal root ganglion neurons from Nav1.8-knock-out mice unveiled an additional tetrodotoxin-resistant Na+ current. The demonstration of its dependence on Nav1.9 provides evidence for a specialized role of Nav1.9, together with Nav1.8, in pain sensation. Although Nax has not been successfully expressed in an exogenous system, recent investigations using relevant native tissues combined with gene-targeting have disclosed their unique \"concentration\"-sensitive but not voltage-sensitive roles. In this context, these emerging views of novel functions mediated by different types of Na+ channels are reviewed, to give a perspective for future research on the expanding family of Na+ channel clones.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"1 1","pages":"365-77"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85361882","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}
To observe the effect of salvianolic acid-B (SalB) against the cytoxicity of amyloid beta peptide (A-beta)(25-35) to PC12 cells, the cells were incubated with A-beta, and the cytoxicity was investigated by MTT, flow cytometry and a cell free apoptotic system. The expression of prostate apoptotic response-4 (Par-4) was detected by Western blot. Aged A-beta 10 micromol/L significantly inhibited the MTT reduction of PC12 cells, SalB1 micromol/L inhibited the toxicity induced by A-beta. In flow cytometric analysis, PC12 cells treated with A-beta exhibited degraded DNA content characteristic of apoptosis cells (1.53% vs 19.9%). PC12 cells pretreated with SalB (10 nmol/L, 100 nmol/L, 1 micromol/L) manifested relatively low proportion of apoptosis (15.7%, 13.5%, 11.8%, respectively). SalB (10 nmol/L - 1 micromol/L) when added at the beginning of the cell free apoptotic reaction had no apparent effect on the nuclei apoptosis. Pretreatment of PC12 cells with SalB largely prevented the increase in Par-4 expression of the cells when they were exposed to A-beta. The results suggest that Par-4 is involved in the protective effect of SalB against A-beta-induced damage in PC12 cells.
{"title":"Prostate apoptosis response-4 involved in the protective effect of salvianolic acid B against amyloid beta peptide-induced damage in PC12 cells.","authors":"M. Tang, Juntian Zhang","doi":"10.1254/JJP.88.422","DOIUrl":"https://doi.org/10.1254/JJP.88.422","url":null,"abstract":"To observe the effect of salvianolic acid-B (SalB) against the cytoxicity of amyloid beta peptide (A-beta)(25-35) to PC12 cells, the cells were incubated with A-beta, and the cytoxicity was investigated by MTT, flow cytometry and a cell free apoptotic system. The expression of prostate apoptotic response-4 (Par-4) was detected by Western blot. Aged A-beta 10 micromol/L significantly inhibited the MTT reduction of PC12 cells, SalB1 micromol/L inhibited the toxicity induced by A-beta. In flow cytometric analysis, PC12 cells treated with A-beta exhibited degraded DNA content characteristic of apoptosis cells (1.53% vs 19.9%). PC12 cells pretreated with SalB (10 nmol/L, 100 nmol/L, 1 micromol/L) manifested relatively low proportion of apoptosis (15.7%, 13.5%, 11.8%, respectively). SalB (10 nmol/L - 1 micromol/L) when added at the beginning of the cell free apoptotic reaction had no apparent effect on the nuclei apoptosis. Pretreatment of PC12 cells with SalB largely prevented the increase in Par-4 expression of the cells when they were exposed to A-beta. The results suggest that Par-4 is involved in the protective effect of SalB against A-beta-induced damage in PC12 cells.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":" 28","pages":"422-7"},"PeriodicalIF":0.0,"publicationDate":"2002-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91414405","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}
In the present study, we examined whether cholinergic agonists would elicit an itch-associated response in mice. When mice were given an intradermal injection of carbachol (1-10 nmol) or bethanechol (0.3-100 nmol) into the rostral back, they showed the dose-dependent increase of scratching. Nicotine (1-10 nmol) showed no effect. Pretreatment with naloxone, but not with terfenadine, significantly suppressed the carbachol-induced scratching. When intradermally co-injected with carbachol, atropine and 4-DAMP but neither methoctramine nor pancuronium significantly inhibited the carbachol-induced scratching. Muscarinic agonists are suggested to produce itch through activation of M3 muscarinic receptors in the skin.
{"title":"Intradermal cholinergic agonists induce itch-associated response via M3 muscarinic acetylcholine receptors in mice.","authors":"Takayuki Miyamoto, H. Nojima, Y. Kuraishi","doi":"10.1254/JJP.88.351","DOIUrl":"https://doi.org/10.1254/JJP.88.351","url":null,"abstract":"In the present study, we examined whether cholinergic agonists would elicit an itch-associated response in mice. When mice were given an intradermal injection of carbachol (1-10 nmol) or bethanechol (0.3-100 nmol) into the rostral back, they showed the dose-dependent increase of scratching. Nicotine (1-10 nmol) showed no effect. Pretreatment with naloxone, but not with terfenadine, significantly suppressed the carbachol-induced scratching. When intradermally co-injected with carbachol, atropine and 4-DAMP but neither methoctramine nor pancuronium significantly inhibited the carbachol-induced scratching. Muscarinic agonists are suggested to produce itch through activation of M3 muscarinic receptors in the skin.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"35 1","pages":"351-4"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87374820","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}
M. Jang, M. Shin, J. Chung, Hyun-Dae Shin, Yeunhee J. Kim, Ee-Hwa Kim, Chang-Ju Kim
Traditionally, Puerariae radix had been used for the treatment of alcohol-related problems. In this study, effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in the dentate gyrus of alcohol-intoxicated Sprague-Dawley rats were investigated via 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Alcohol administration was shown to inhibit the numbers of both BrdU-positive and NADPH-d-positive cells, while Puerariae radix treatment was shown to increase those numbers. It is possible that nitric oxide, which might play an important role in the regulation of cell proliferation, is a major target of the toxic effects of alcohol.
{"title":"Effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in dentate gyrus of alcohol-intoxicated Sprague-Dawley rats.","authors":"M. Jang, M. Shin, J. Chung, Hyun-Dae Shin, Yeunhee J. Kim, Ee-Hwa Kim, Chang-Ju Kim","doi":"10.1254/JJP.88.355","DOIUrl":"https://doi.org/10.1254/JJP.88.355","url":null,"abstract":"Traditionally, Puerariae radix had been used for the treatment of alcohol-related problems. In this study, effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in the dentate gyrus of alcohol-intoxicated Sprague-Dawley rats were investigated via 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Alcohol administration was shown to inhibit the numbers of both BrdU-positive and NADPH-d-positive cells, while Puerariae radix treatment was shown to increase those numbers. It is possible that nitric oxide, which might play an important role in the regulation of cell proliferation, is a major target of the toxic effects of alcohol.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"20 1","pages":"355-8"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73524533","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. Matsuo, E. Ishikawa, M. Ohta, Y. Shibouta, Y. Ishimura, Y. Imura, Y. Sugiyama
Spontaneously hypercholesterolemic (SHC) rats exhibit hypercholesterolemia, proteinuria and focal glomerulosclerosis with age, and they finally die as a result of renal failure. In this study, the renoprotective effects of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, and enalapril, an angiotensin I converting enzyme inhibitor, were examined in SHC rats. Candesartan cilexetil (0.1 and 1 mg /kg) and enalapril (10 mg/kg) were administered orally to 10-week-old SHC rats for a 6-week period. Candesartan cilexetil (1 mg/kg) and enalapril (10 mg/kg) significantly inhibited proteinuria and hypercholesterolemia to a similar extent. In untreated 16-week-old SHC rats, glomerulosclerosis, basophilic change, cast formation and interstitial mononuclear cell infiltration were observed. Candesartan cilexetil (1 mg/kg) inhibited all of these histological changes. Enalapril inhibited glomerulosclerosis and cast formation. These results show that candesartan cilexetil and enalapril have renal protective effects in SHC rats. Thus, angiotensin II might play an important role in renal pathogenesis in a model of focal glomerulosclerosis with hypercholesterolemia.
{"title":"Renal protective effect of candesartan cilexetil in spontaneously hypercholesterolemic rats.","authors":"T. Matsuo, E. Ishikawa, M. Ohta, Y. Shibouta, Y. Ishimura, Y. Imura, Y. Sugiyama","doi":"10.1254/JJP.88.300","DOIUrl":"https://doi.org/10.1254/JJP.88.300","url":null,"abstract":"Spontaneously hypercholesterolemic (SHC) rats exhibit hypercholesterolemia, proteinuria and focal glomerulosclerosis with age, and they finally die as a result of renal failure. In this study, the renoprotective effects of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, and enalapril, an angiotensin I converting enzyme inhibitor, were examined in SHC rats. Candesartan cilexetil (0.1 and 1 mg /kg) and enalapril (10 mg/kg) were administered orally to 10-week-old SHC rats for a 6-week period. Candesartan cilexetil (1 mg/kg) and enalapril (10 mg/kg) significantly inhibited proteinuria and hypercholesterolemia to a similar extent. In untreated 16-week-old SHC rats, glomerulosclerosis, basophilic change, cast formation and interstitial mononuclear cell infiltration were observed. Candesartan cilexetil (1 mg/kg) inhibited all of these histological changes. Enalapril inhibited glomerulosclerosis and cast formation. These results show that candesartan cilexetil and enalapril have renal protective effects in SHC rats. Thus, angiotensin II might play an important role in renal pathogenesis in a model of focal glomerulosclerosis with hypercholesterolemia.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"71 1","pages":"300-6"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90445146","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 have examined the functional significance of the naturally occurring mutation at position 64 of human beta3-adrenergic receptor (beta3AR), which changes the amino acid from tryptophan to arginine (W64R-beta3AR). The affinities of betaAR agonists for W64R-beta3AR expressed in COS-7 cells were not significantly different from those for wild type beta3AR. When two receptors are expressed at various expression levels, and stimulated with CGP12177A, they showed essentially the same EC50 values and maximal responses. Overexpression of Gi and Go, or the treatment with pertussis toxin did not affect the agonist-induced cAMP response, suggesting that Gi and Go did not contribute to the beta3AR-induced cAMP response. However, the enhanced cAMP response was observed when W64R-beta3AR was coexpressed with the adenylyl cyclase type III isoform, and stimulated by CGP12177A and isoproterenol. These results indicate that the cAMP response of W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed.
{"title":"Enhanced cAMP response of naturally occurring mutant of human beta3-adrenergic receptor.","authors":"M. Isogaya, T. Nagao, H. Kurose","doi":"10.1254/JJP.88.314","DOIUrl":"https://doi.org/10.1254/JJP.88.314","url":null,"abstract":"We have examined the functional significance of the naturally occurring mutation at position 64 of human beta3-adrenergic receptor (beta3AR), which changes the amino acid from tryptophan to arginine (W64R-beta3AR). The affinities of betaAR agonists for W64R-beta3AR expressed in COS-7 cells were not significantly different from those for wild type beta3AR. When two receptors are expressed at various expression levels, and stimulated with CGP12177A, they showed essentially the same EC50 values and maximal responses. Overexpression of Gi and Go, or the treatment with pertussis toxin did not affect the agonist-induced cAMP response, suggesting that Gi and Go did not contribute to the beta3AR-induced cAMP response. However, the enhanced cAMP response was observed when W64R-beta3AR was coexpressed with the adenylyl cyclase type III isoform, and stimulated by CGP12177A and isoproterenol. These results indicate that the cAMP response of W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"57 1","pages":"314-8"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81497905","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. Hashimoto, Yuuki Nakano, M. Yamashita, Yang-Il Fang, H. Ohata, K. Momose
Inhalation of oleoyl lysophosphatidic acid (LPA) induced airway hyperresponsiveness to acetylcholine (ACh). In contrast, palmitoyl and stearoyl LPA exerted minimal effects. Airway hyperresponsiveness was inhibited by inhalation of Y-27632, an inhibitor of Rho-associated protein kinase (ROCK). Mepyramine, an H1 histamine receptor antagonist and ketotifen, an inhibitor of histamine release and H1 histamine receptor antagonist, also inhibited airway hyperresponsiveness induced by LPA; however, aspirin failed to attenuate this response. The incubation of lung fragments with LPA gave rise to releases in histamine. On the other hand, LPA produced no significant changes on the smooth muscle contraction evoked by ACh. These findings suggest that LPA-induced airway hyperresponsiveness is attributable to activation of the Rho/ROCK-mediated pathway via endothelial cell differentiation gene (EDG) receptors, probably EDG 7. Moreover, histamine release may be involved.
{"title":"Role of Rho-associated protein kinase and histamine in lysophosphatidic acid-induced airway hyperresponsiveness in guinea pigs.","authors":"T. Hashimoto, Yuuki Nakano, M. Yamashita, Yang-Il Fang, H. Ohata, K. Momose","doi":"10.1254/JJP.88.256","DOIUrl":"https://doi.org/10.1254/JJP.88.256","url":null,"abstract":"Inhalation of oleoyl lysophosphatidic acid (LPA) induced airway hyperresponsiveness to acetylcholine (ACh). In contrast, palmitoyl and stearoyl LPA exerted minimal effects. Airway hyperresponsiveness was inhibited by inhalation of Y-27632, an inhibitor of Rho-associated protein kinase (ROCK). Mepyramine, an H1 histamine receptor antagonist and ketotifen, an inhibitor of histamine release and H1 histamine receptor antagonist, also inhibited airway hyperresponsiveness induced by LPA; however, aspirin failed to attenuate this response. The incubation of lung fragments with LPA gave rise to releases in histamine. On the other hand, LPA produced no significant changes on the smooth muscle contraction evoked by ACh. These findings suggest that LPA-induced airway hyperresponsiveness is attributable to activation of the Rho/ROCK-mediated pathway via endothelial cell differentiation gene (EDG) receptors, probably EDG 7. Moreover, histamine release may be involved.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"478 1","pages":"256-61"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74709589","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}
A. Sugiyama, A. Takahara, Y. Satoh, M. Yoneyama, Y. Saegusa, K. Hashimoto
Cardiac effects of 10 kinds of clinically available Kampo medicines were investigated: Kakkon-to (TJ-1), Dai-saiko-to (TJ-8), Boi-ogi-to (TJ-20), Chorei-to (TJ-40), Rokumi-gan (TJ-87), Tsu-do-san (TJ-105), Gosha-jinki-gan (TJ-107), San'o-shashin-to (TJ-113), Sairei-to (TJ-114) and Inchin-gorei-san (TJ-117). Chronotropic and inotropic effects were studied using canine isolated, blood-perfused heart preparations, while subcellular mechanisms were analyzed by measuring the drug-induced changes of the adenylate cyclase activity in the canine ventricular membrane preparation. Intracoronary injections of TJ-1, TJ-20, TJ-105 and TJ-113 increased the sinoatrial rate and developed tension of papillary muscle in a dose-related manner, which was significantly attenuated by the pretreatment of the preparations with beta-blocker propranolol. Meanwhile, the other extracts hardly affected these parameters. TJ-1, TJ-20 and TJ-113 increased the adenylate cyclase activity in a dose-related manner, but their potency was significantly less compared with that by an equivalent concentration of isoproterenol. Moreover, TJ-105 did not increase the adenylate cyclase activity. These results suggest that the positive chronotropic and inotropic effects of TJ-1, TJ-20, TJ- 105 and TJ-113 may be exerted through the direct stimulation of the beta-adrenoceptor and/or the norepinephrine release from the postganglionic nerve terminals in the heart.
研究了10种临床使用的汉布药:Kakkon-to (TJ-1)、daisaiko -to (TJ-8)、Boi-ogi-to (TJ-20)、Chorei-to (TJ-40)、Rokumi-gan (TJ-87)、tsudo - San (TJ-105)、goha -jinki-gan (TJ-107)、San'o-shashin-to (TJ-113)、saiei -to (TJ-114)和injin -gorei- San (TJ-117)的心脏作用。研究了犬离体血灌注心脏制剂的变时和变肌力作用，并通过测量犬心室膜制剂中腺苷酸环化酶活性的药物诱导变化分析了亚细胞机制。冠状动脉内注射TJ-1、TJ-20、TJ-105和TJ-113使窦房率升高，乳头肌张力呈剂量相关，经β受体阻滞剂心得安预处理后明显减弱。而其他提取物对这些参数几乎没有影响。TJ-1、TJ-20和TJ-113均能增加腺苷酸环化酶的活性，但与同等浓度的异丙肾上腺素相比，TJ-1、TJ-20和TJ-113的效力显著降低。此外，TJ-105没有增加腺苷酸环化酶的活性。这些结果提示，TJ-1、TJ-20、TJ- 105和TJ-113的正性变时性和正性肌力作用可能是通过直接刺激β -肾上腺素受体和/或从心脏神经节后神经末梢释放去甲肾上腺素来发挥的。
{"title":"Cardiac effects of clinically available Kampo medicine assessed with canine isolated, blood-perfused heart preparations.","authors":"A. Sugiyama, A. Takahara, Y. Satoh, M. Yoneyama, Y. Saegusa, K. Hashimoto","doi":"10.1254/JJP.88.307","DOIUrl":"https://doi.org/10.1254/JJP.88.307","url":null,"abstract":"Cardiac effects of 10 kinds of clinically available Kampo medicines were investigated: Kakkon-to (TJ-1), Dai-saiko-to (TJ-8), Boi-ogi-to (TJ-20), Chorei-to (TJ-40), Rokumi-gan (TJ-87), Tsu-do-san (TJ-105), Gosha-jinki-gan (TJ-107), San'o-shashin-to (TJ-113), Sairei-to (TJ-114) and Inchin-gorei-san (TJ-117). Chronotropic and inotropic effects were studied using canine isolated, blood-perfused heart preparations, while subcellular mechanisms were analyzed by measuring the drug-induced changes of the adenylate cyclase activity in the canine ventricular membrane preparation. Intracoronary injections of TJ-1, TJ-20, TJ-105 and TJ-113 increased the sinoatrial rate and developed tension of papillary muscle in a dose-related manner, which was significantly attenuated by the pretreatment of the preparations with beta-blocker propranolol. Meanwhile, the other extracts hardly affected these parameters. TJ-1, TJ-20 and TJ-113 increased the adenylate cyclase activity in a dose-related manner, but their potency was significantly less compared with that by an equivalent concentration of isoproterenol. Moreover, TJ-105 did not increase the adenylate cyclase activity. These results suggest that the positive chronotropic and inotropic effects of TJ-1, TJ-20, TJ- 105 and TJ-113 may be exerted through the direct stimulation of the beta-adrenoceptor and/or the norepinephrine release from the postganglionic nerve terminals in the heart.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"473 1","pages":"307-13"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79087729","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}
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