title: Differential effects of the calcium entry blocker D 600 on contractions of rat and guinea-pig aortas, elicited by various alpha-1 adrenoceptor agonists.
abstract: Contractions of rat and guinea-pig aortas to the alpha-adrenoceptor agonists I-norepinephrine, cirazoline , St 587, clonidine and Sgd 101/75 and the effect of calcium entry blockade by D 600 on the responses were evaluated. In rat aorta, D-600 (10(-8) to 10(-5) M) effectively and concentration-dependently reduced the maximal responses to St 587, clonidine and Sgd 101/75 (maximal percentage inhibition 84 +/- 2.1, 86 +/- 4.1 and 65 +/- 2.8, n = 5-6, respectively) in contrast to those of I-norepinephrine and cirazoline (maximal percentage inhibition 23 +/- 2.1 and 21 +/- 4.1, n = 6, respectively). Reducing the receptor number on rat aorta by approximately 85% by means of the irreversible blocker dibenamine did not result in a greater sensitivity of norepinephrine-induced contractions toward D 600. Prazosin was found 800 to 1000 times more potent than yohimbine in antagonizing the contractile effects of St 587, clonidine and cirazoline on rat and guinea-pig aortas. No difference existed between the pA2 values of prazosin and yohimbine against the different agonists; the pA2 values of prazosin and yohimbine were significantly higher in rat aorta than those in guinea-pig aorta. The results can be explained by assuming the existence of two different agonist recognition sites on the alpha-1 adrenoceptor on rat aorta, whereas the alpha-1 adrenoceptor on guinea-pig aorta contains one agonist recognition site only. The architecture of the alpha-1 adrenoceptor on rat aorta must therefore be different from that in guinea-pig aorta.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D005711:Gallopamil; D014700:Verapamil; D002118:Calcium; D011224:Prazosin