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.
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)
Sulpizio
A
A
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Hieble
J P
JP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D009543:Nifedipine; D002118:Calcium