Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta.
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.
Brahmadevara
Nataraj
N
Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, Scotland, UK.
Shaw
Angus M
AM
MacDonald
Allan
A
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3