Beta 1-, beta 2- and atypical beta-adrenoceptor-mediated relaxation in rat isolated aorta.
beta-adrenoceptor-mediated relaxation was investigated in ring preparations of rat isolated thoracic aorta. Rings were pre-constricted with a sub-maximal concentration of noradrenaline (1 microM) and relaxant responses to cumulative concentrations of beta-adrenoceptor agonists obtained. The concentration-response curve (CRC) to isoprenaline was shifted to the right by propranolol (0.3 microM) with a steepening of the slope. Estimation of the magnitude of the shift from EC(50) values gave a pA(2) of 7.6. Selective beta(1)- and beta(2)-adrenoceptor antagonists, CGP 20712A (0.1 microM) and ICI 118551 (0.1 microM), respectively, produced 4 and 14 fold shifts of the isoprenaline CRC. Atypical beta-adrenoceptor agonists also produced concentration-dependent relaxation of aortic rings. The order of potency of the beta-adrenoceptor agonists was (-log EC(50)): isoprenaline (6. 25)>cyanopindolol (5.59)>isoprenaline+propranolol (5.11)>CGP 12177A (4.40)>ZD 2079 (4.24)>ZM 215001 (4.07)>BRL 37344 (3.89). Relaxation to CGP 12177A and ZM 215001 was unaffected by propranolol (0.3 microM). SR 59230A (</=1 microM) and cyanopindolol (1 microM), beta(3)-adrenoceptor antagonists, had no effect on the isoprenaline (in the presence of propranolol) or CGP 12177A CRCs. Bupranolol and CGP 20712A, at microM concentrations (beta(4)-adrenceptor antagonists), inhibited responses to isoprenaline (in the presence of propranolol) and CGP 12177A. In conclusion, atypical beta-adrenoceptors co-exist with beta(1)- and beta(2)-adrenoceptors in rat aorta. Although non-conventional partial agonists and selective beta(3)-adrenoceptor agonist cause relaxation, the vascular atypical beta-adrenoceptor does not appear to correspond to the beta(3)-adrenoceptor. There are, however, similarities with the putative beta(4)-adrenoceptor.
Brawley
L
L
School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA.
Shaw
A M
AM
MacDonald
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002046:Bupranolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000145:classification* / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D013379:Substrate Specificity; D014665:Vasodilator Agents / Q000494:pharmacology
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014665:Vasodilator Agents; C047975:cyanopindolol; D002046:Bupranolol; D011433:Propranolol; D010869:Pindolol; C049763:CGP 20712A; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine