Alpha(1)-adrenoceptor subtypes mediating contractions of the rat mesenteric artery.
The alpha(1)-adrenoceptor subtype(s) mediating contractions of the rat mesenteric artery were investigated using the agonists methoxamine, cirazoline, P7480 (N-(4-pyridinyl)-1H-indol-1-amine) and subtype-selective antagonists including BMY 7378 (8-(-2(-4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4, 5)decane-7,9,dione dihydrochloride). pA(2) or apparent pK(B) values of antagonists against methoxamine contractions correlated best with its pK(i) values at the cloned alpha(1b)-(0.88), with cirazoline, antagonists affinities correlated equally well with those at alpha(1a)-(0.79) or the alpha(1b)-(0.81) while with P7480 antagonist affinities correlated best with the alpha(1d)-adrenoceptor subtype (0.94). The low affinity estimate for 5-methylurapidil (7.5) against the alpha(1a)-selective cirazoline suggests an alpha(1A)-subtype mediating contraction is unlikely. Shallow Schild plot slopes of subtype selective antagonists against all three agonists are consistent with heterogeneity of alpha(1)-adrenoceptors. P7480 (putative alpha(1D)-adrenoceptor-selective) acts primarily at this subtype and at another which is more likely to be an alpha(1B)- than an alpha(1A)-adrenoceptor. The results with both agonists and antagonists are consistent with contractions of the rat mesenteric artery being mediated via the alpha(1D)- and possibly alpha(1B)-adrenoceptor.
Hussain
M B
MB
Department of Pharmacology, University College London, Gower Street, London, UK.
Marshall
I
I
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007217:Indoramin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D010075:Oxathiins / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D007211:Indoles; D010075:Oxathiins; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D007217:Indoramin; C096037:N-(4-pyridinyl)-1H-indol-1-amine; C057446:5-methylurapidil; D010656:Phenylephrine; C050877:benoxathian; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D008729:Methoxamine; C053428:BMY 7378; C014282:cirazoline; D011224:Prazosin