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Lack of a pharmacological distinction between alpha-1 adrenoceptors mediating intracellular calcium-dependent and independent contractions to sympathetic nerve stimulation in the perfused rat caudal artery

A Sulpizio and JP Hieble

Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.

The contractile response of the rat caudal artery to field stimulation occurred in two phases; an initial rapidly developing contraction (phasic) and a subsequent more slowly developing contraction (tonic). Phenoxybenzamine, an irreversible antagonist, and prazosin, a competitive antagonist at the alpha-1 adrenoceptor, nonselectively inhibited both contractile phases. Ryanodine, an inhibitor of intracellular calcium release, selectively inhibited the phasic component, whereas nifedipine, a membrane calcium channel blocker, selectively inhibited the tonic component. These data demonstrate that both contractile phases are mediated by alpha-1 adrenoceptors and the phases are distinguished by the calcium source mobilized; intracellular stores of calcium are mobilized during the phasic component and extracellular calcium is mobilized during the tonic component. Inasmuch as alpha-1 adrenoceptors on nonvascular smooth muscle may be divided into alpha-1A and alpha-1B subtypes based on ability to open membrane calcium channels or ability to stimulate intracellular calcium release, respectively, we characterized the alpha-1 adrenoceptor mediating the contraction to determine whether a specific subtype was coupled to each phase. WB4101, a marginally alpha-1A adrenoceptor selective antagonist, 5-methyl-urapidil, a highly alpha-1A adrenoceptor selective antagonist and chloroethylclonidine, a highly alpha-1B adrenoceptor selective antagonist, all inhibited both contractile phases. These findings indicate that endogenous norepinephrine contracts the rat caudal artery via alpha-1 adrenoceptors that mobilize both the release of intracellular calcium and the influx of calcium through membrane channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 257, Issue 3, pp. 1045-1052, 06/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




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