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)
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
A
A
Sulpizio
J P
JP
Hieble
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