title: Heterogeneity of postjunctional alpha 1-adrenoceptors in mammalian aortae: subclassification based on chlorethylclonidine, WB 4101 and nifedipine.
abstract: The effects of chlorethylclonidine, WB 4101 and nifedipine on norepinephrine-induced contractions of rat, guinea-pig, rabbit and dog aortae were investigated in order to characterize the alpha 1-adrenoceptor subtype(s) present in the aortae of these different species. The putative alpha 1A-adrenoceptor antagonist, WB 4101, was significantly more potent in the rat aorta compared to the rabbit, guinea-pig and dog aortae which were not significantly different from each other. The calcium channel antagonist, nifedipine (1 microM), had little or no effect on norepinephrine-induced contractions in aortic segments from the rabbit, guinea pig and dog; whereas in the rat aorta, nifedipine significantly inhibited the response to norepinephrine. Based on the studies with WB 4101 and nifedipine, alpha 1-adrenoceptors in rat aorta would be tentatively classified as alpha 1A-adrenoceptors, whereas those in the guinea-pig, rabbit and dog aortae would be of the alpha 1B-adrenoceptor subtype. The putative irreversible alpha 1B-adrenoceptor antagonist, chlorethylclonidine, inhibited the response to norepinephrine in aortae from all species, but to dramatically different degrees. The response to norepinephrine was inhibited by 500-fold and 450-fold by chlorethylclonidine in the rat and dog aortae, respectively, whereas in the guinea-pig and rabbit aortae, the potency of norepinephrine was reduced by only 3- and 20-fold, respectively. Thus, based on studies with chlorethylclonidine, alpha 1-adrenoceptors in the rat and dog aortae would be classified as alpha 1B-adrenoceptors (i.e., chlorethylclonidine-sensitive), whereas alpha 1A-adrenoceptors (chlorethylclonidine-insensitive) would predominate in the guinea-pig aorta, and possibly both alpha 1A- and alpha 1B-adrenoceptors would coexist in the rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
authors.forename: M A
authors.initials: MA
authors.lastname: Oriowo
authors.forename: R R
authors.initials: RR
authors.lastname: Ruffolo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification* / Q000187:drug effects / Q000502:physiology
chemical_list: D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009543:Nifedipine; D003000:Clonidine; D009638:Norepinephrine