{"title":"应用BRL 37344、cyanopindolol和sr59230a对兔离体空肠非典型β-肾上腺素受体的表征","authors":"A. MacDonald, K. Watt","doi":"10.1046/j.1365-2680.1999.00121.x","DOIUrl":null,"url":null,"abstract":"<p> <b>1</b> The present study was carried out to further investigate the nature of the β-adrenoceptor in rabbit jejunum using BRL 37344, a selective β<sub>3</sub>-adrenoceptor agonist, cyanopindolol, a β-adrenoceptor antagonist with blocking activity at β<sub>3</sub>-adrenoceptors and SR 59230A, a new selective β<sub>3</sub>-adrenoceptor antagonist.</p><p> <b>2</b> Isoprenaline produced a concentration-dependent inhibition of the spontaneous contractions of rabbit jejunum with a pD<sub>2</sub> of 7.14. Propranolol (1 μ<span>m</span>) shifted the isoprenaline concentration-response curve (CRC) to the right with a concentration-ratio of 5.85, considerably less than would be expected for an action at classical β-adrenoceptors (estimated pA<sub>2</sub> 6.66).</p><p> <b>3</b> BRL 37344 also produced a concentration-dependent inhibition of spontaneous contractions with a pD<sub>2</sub> of 7.41. The BRL 37344 CRC was unaffected by propranolol (1 μ<span>m</span>).</p><p> <b>4</b> In the presence of propranolol (1 μ<span>m</span>), cyanopindolol (1 μ<span>m</span>) shifted the isoprenaline CRC to the right (concentration-ratio of 21). Cyanopindolol also shifted the BRL 37344 CRC to the right (concentration-ratio of 38). These shifts are consistent with the affinity of cyanopindolol for β<sub>3</sub>-adrenoceptors (estimated pA<sub>2</sub> values of 7.27 and 7.38 against isoprenaline and BRL 37344, respectively).</p><p> <b>5</b> In the presence of propranolol (1 μ<span>m</span>), SR 59230A produced a concentration-dependent rightward shift of the isoprenaline CRC. The Schild plot gave a pA<sub>2</sub> value of 7.16, although the slope of the regression line was significantly different from unity (0.65). SR 59230A also produced a concentration-dependent shift of the BRL 37344 CRC. The Schild plot gave a pA<sub>2</sub> of 7.58 with the slope of the regression line not significantly different from unity (0.81).</p><p> <b>6</b> The presence of β<sub>3</sub>-adrenoceptors mediating relaxation of spontaneous contractions in rabbit jejunum is supported by the relatively poor antagonism of isoprenaline by propranolol, the relaxant effect of BRL 37344 and the antagonism of isoprenaline and BRL 37344 by cyanopindolol and SR 59230A. The lack of simple competitive antagonism of isoprenaline, but not BRL 37344, by SR 59230A may suggest more than one population of atypical β-adrenoceptor.</p>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2008-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-2680.1999.00121.x","citationCount":"9","resultStr":"{\"title\":\"Characterisation of the atypical β-adrenoceptor in rabbit isolated jejunum using BRL 37344, cyanopindolol and SR 59230A\",\"authors\":\"A. MacDonald, K. Watt\",\"doi\":\"10.1046/j.1365-2680.1999.00121.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p> <b>1</b> The present study was carried out to further investigate the nature of the β-adrenoceptor in rabbit jejunum using BRL 37344, a selective β<sub>3</sub>-adrenoceptor agonist, cyanopindolol, a β-adrenoceptor antagonist with blocking activity at β<sub>3</sub>-adrenoceptors and SR 59230A, a new selective β<sub>3</sub>-adrenoceptor antagonist.</p><p> <b>2</b> Isoprenaline produced a concentration-dependent inhibition of the spontaneous contractions of rabbit jejunum with a pD<sub>2</sub> of 7.14. Propranolol (1 μ<span>m</span>) shifted the isoprenaline concentration-response curve (CRC) to the right with a concentration-ratio of 5.85, considerably less than would be expected for an action at classical β-adrenoceptors (estimated pA<sub>2</sub> 6.66).</p><p> <b>3</b> BRL 37344 also produced a concentration-dependent inhibition of spontaneous contractions with a pD<sub>2</sub> of 7.41. The BRL 37344 CRC was unaffected by propranolol (1 μ<span>m</span>).</p><p> <b>4</b> In the presence of propranolol (1 μ<span>m</span>), cyanopindolol (1 μ<span>m</span>) shifted the isoprenaline CRC to the right (concentration-ratio of 21). Cyanopindolol also shifted the BRL 37344 CRC to the right (concentration-ratio of 38). These shifts are consistent with the affinity of cyanopindolol for β<sub>3</sub>-adrenoceptors (estimated pA<sub>2</sub> values of 7.27 and 7.38 against isoprenaline and BRL 37344, respectively).</p><p> <b>5</b> In the presence of propranolol (1 μ<span>m</span>), SR 59230A produced a concentration-dependent rightward shift of the isoprenaline CRC. The Schild plot gave a pA<sub>2</sub> value of 7.16, although the slope of the regression line was significantly different from unity (0.65). SR 59230A also produced a concentration-dependent shift of the BRL 37344 CRC. The Schild plot gave a pA<sub>2</sub> of 7.58 with the slope of the regression line not significantly different from unity (0.81).</p><p> <b>6</b> The presence of β<sub>3</sub>-adrenoceptors mediating relaxation of spontaneous contractions in rabbit jejunum is supported by the relatively poor antagonism of isoprenaline by propranolol, the relaxant effect of BRL 37344 and the antagonism of isoprenaline and BRL 37344 by cyanopindolol and SR 59230A. The lack of simple competitive antagonism of isoprenaline, but not BRL 37344, by SR 59230A may suggest more than one population of atypical β-adrenoceptor.</p>\",\"PeriodicalId\":100151,\"journal\":{\"name\":\"Autonomic and Autacoid Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2008-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1046/j.1365-2680.1999.00121.x\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autonomic and Autacoid Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2680.1999.00121.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2680.1999.00121.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Characterisation of the atypical β-adrenoceptor in rabbit isolated jejunum using BRL 37344, cyanopindolol and SR 59230A
1 The present study was carried out to further investigate the nature of the β-adrenoceptor in rabbit jejunum using BRL 37344, a selective β3-adrenoceptor agonist, cyanopindolol, a β-adrenoceptor antagonist with blocking activity at β3-adrenoceptors and SR 59230A, a new selective β3-adrenoceptor antagonist.
2 Isoprenaline produced a concentration-dependent inhibition of the spontaneous contractions of rabbit jejunum with a pD2 of 7.14. Propranolol (1 μm) shifted the isoprenaline concentration-response curve (CRC) to the right with a concentration-ratio of 5.85, considerably less than would be expected for an action at classical β-adrenoceptors (estimated pA2 6.66).
3 BRL 37344 also produced a concentration-dependent inhibition of spontaneous contractions with a pD2 of 7.41. The BRL 37344 CRC was unaffected by propranolol (1 μm).
4 In the presence of propranolol (1 μm), cyanopindolol (1 μm) shifted the isoprenaline CRC to the right (concentration-ratio of 21). Cyanopindolol also shifted the BRL 37344 CRC to the right (concentration-ratio of 38). These shifts are consistent with the affinity of cyanopindolol for β3-adrenoceptors (estimated pA2 values of 7.27 and 7.38 against isoprenaline and BRL 37344, respectively).
5 In the presence of propranolol (1 μm), SR 59230A produced a concentration-dependent rightward shift of the isoprenaline CRC. The Schild plot gave a pA2 value of 7.16, although the slope of the regression line was significantly different from unity (0.65). SR 59230A also produced a concentration-dependent shift of the BRL 37344 CRC. The Schild plot gave a pA2 of 7.58 with the slope of the regression line not significantly different from unity (0.81).
6 The presence of β3-adrenoceptors mediating relaxation of spontaneous contractions in rabbit jejunum is supported by the relatively poor antagonism of isoprenaline by propranolol, the relaxant effect of BRL 37344 and the antagonism of isoprenaline and BRL 37344 by cyanopindolol and SR 59230A. The lack of simple competitive antagonism of isoprenaline, but not BRL 37344, by SR 59230A may suggest more than one population of atypical β-adrenoceptor.
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