Literature DB >> 12522078

Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta.

Nataraj Brahmadevara1, Angus M Shaw, Allan MacDonald.   

Abstract

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 phenylephrine-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 (< or =1 microM). CL 316243 (< or =100 microM) failed to produce relaxation. In PGF(2alpha)-constricted rings only SR 58611A produced relaxation, which was not affected by SR 59230A (< or =3 microM). 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 (< or =1 microM) or by CGP 20712A (10 microM), 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) approximately 38;SR 59230A (5.47) approximately 38;cyanopindolol (5.47)>pindolol (5.30)>alprenolol (5.10)>propranolol (4.83)>ICI 118551 (4.60)>CGP 12177A (4.38) approximately 38;CGP 20712A (4.35). Bupranolol (100 microM), alprenolol (30 microM), propranolol (100 microM) and SR 59230A (10 microM) 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.

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Year:  2003        PMID： 12522078      PMCID： PMC1573643          DOI： 10.1038/sj.bjp.0705017

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN： 0007-1188            Impact factor:   8.739


  37 in total

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10.  Atypical beta-adrenoceptors, different from beta 3-adrenoceptors and probably from the low-affinity state of beta 1-adrenoceptors, relax the rat isolated mesenteric artery.

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