Evidence against β3-adrenoceptors or low affinity state of β1-adrenoceptors mediating relaxation in rat isolated aorta

被引：43

作者：

Brahmadevara, N ^{[1
]}

Shaw, AM ^{[1
]}

MacDonald, A ^{[1
]}

机构：

[1] Glasgow Caledonian Univ, Sch Life Sci, Dept Biol & Biomed Sci, Glasgow G4 0BA, Lanark, Scotland

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2003年 / 138卷 / 01期

关键词：

beta-adrenoceptors; beta(3)-adrenoceptors; putative beta(4)-adrenoceptors; low affinity state of beta(1)-adrenoceptors; rat aorta; beta(3)-adrenoceptor agonists; non-conventional partial agonists; beta-adrenoceptor antagonists;

D O I：

10.1038/sj.bjp.0705017

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 The presence of beta(3)-adrenoceptors and the low affinity state of the beta(1)-adrenoceptor (formerly 'putative beta(4)-adrenoceptor') was investigated in ring preparations of rat isolated aorta preconstricted with phenylephrine or prostaglandin F-2alpha (PGF(2alpha)). Relaxant responses to isoprenaline, selective beta(3)-adrenoceptor agonists (BRL 37344, SR 58611A. CL 316243) and non-conventional partial agonists (CGP 12177A, cyanopindolol, pindolol) were obtained. 2 In phenylephrine-constricted, but not PGF(2alpha)-constricted rings, relaxations to isoprenaline showed a propranolol-resistant component. 3 In phonylephrine-constricted rings. relaxations to BRL 37344 (pEC(50), 4.64) and SR 58611A (pEC(50), 4.94) were not antagonized by the selective beta(3)-adrenoceptor antagonist SR 59230A (less than or equal to1 muM). CL 316243 (less than or equal to 100 muM) failed to produce relaxation. In PGF(2alpha)-constricted rings only SR 58611A produced relaxation. which was not affected by SR 59230A (less than or equal to 3 muM). 4 Non-conventional partial agonists produced relaxation in phenylephrine-constricted but not PGF(2alpha)-constricted rings. The relaxation to CGP 12177A was unaffected by SR 59230A (less than or equal to 1 muM) or by CGP 20712A (10 muM), reported to block the low affinity state of the beta(1)-adrenoceptor. 5 beta-adrenoceptor antagonists also produced relaxation in phenylephrine-constricted rings with an order of potency of (pEC(50) values): bupranolol (5.5) approximate to SR 59230A (5.47) approximate to cyanopindolol (5.47) > pindolol (5.30) > alprenolol (5.10) > propranolol (4.83) > ICI 118551 (4.60) > CGP 12177A (4.38) approximate to CGP 20712A (4.35). Bupranolol (100 muM). alprenolol (30 muM). propranolol (100 muM) and SR 59230A (10 muM) produced no relaxation in PGF(2alpha)-constricted rings, 6 These results provide no evidence for the presence of functional beta(3)-adrenoceptors or the low affinity, state of the beta(1)-adrenoceptor in rat aorta.

引用

页码：99 / 106

页数：8

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