Sources of calcium and alpha 1-adrenoceptor-mediated contraction in rat tail artery.
1. The relative importance of intracellular and extracellular Ca2+ on alpha 1-adrenoceptor-mediated contraction by noradrenaline and St-587 has been studied and correlated with the binding characteristics in intact tail artery from Sprague-Dawley rats. 2. Noradrenaline and St-587 behaved as full agonists inducing a concentration-dependent vasoconstriction. 3. Nifedipine (1 microM and 10 microM) blocked by 50% (P < 0.001) and 75% (P < 0.001) respectively, the maximum contraction (Emax) induced by St-587. Nevertheless, to reach 40% inhibition of Emax on noradrenaline responses (P < 0.01), 10 microM nifedipine was necessary. 4. Both agonists induced a concentration-dependent accumulation of inositol phosphates. Noradrenaline behaved as a full agonist and St-587 as a partial agonist for this response. 5. [3H]-prazosin binding to intact tail artery rings was saturable and of high affinity (KD = 4.44 +/- 0.46 nM; Bmax = 36.35 +/- 4.22 fmol mg-1 tissue). 6. Competition curves for inhibition of specific [3H]-prazosin binding by WB-4101 suggest that the rat tail artery contains two alpha 1-adrenoceptor subtypes in an approximate ratio of 60:40. 7. After irreversible alkylation of alpha 1B-adrenoceptors with 100 microM chloroethylclonidine (CEC), nifedipine (1 microM) influenced to a greater extent the St-587- than the noradrenaline-induced contraction. 8. Our results indicate that the degree of participation of intracellular and extracellular Ca2+ sources, on the alpha 1-adrenoceptor-mediated contraction, depends on the agonist used. The two alpha 1-adrenoceptor subtypes observed in binding experiments seem to be unrelated to the Ca2+ sources used for contraction.
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Department de Farmacologia i Terapèutica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013623:Tail / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D002118:Calcium