Pharmacological characterization of α1-adrenoceptor subtypes in the bovine tail artery

The purpose of this study was to identify the alpha(1)-adrenoreceptor subtypes present in the bovine tail artery which mediate contractions to adrenergic agonists. A61603, an alpha(1A)-selective agonist, was more potent compared with norepinephrine and phenylephrine. The pK(A) value of A61603 was 6.93 +/- 0.19 muM (n = 6). Antagonists, BMY 7378, WB 4101 and 5-methylurapidil, caused a parallel shift to the right of the concentration-response curve to A61603 with pA(2) values of 6.62, 9.27 and 8.86, respectively. Prazosin, BMY 7378 and WB 4101 inhibited phenylephrine induced contraction with pA(2) values of 9.47, 7.17 and 9.73, respectively. The pA(2) values obtained for 5-methylurapidil, WB 4101, BMY 7378 and prazosin against alpha(1)-adrenoceptor agonists were significantly correlated with pK(i) values (Zhu, Zhang & Han, 1997, Eur. J. Pharmacol. 329, 55-61) for the cloned alpha(1a)-adrenoceptor but not with the cloned alpha(1b)- or alpha(1d)-adrenoceptor. BMY 7378, a selective alpha(1D)-adrenoceptor antagonist, was significantly more potent against the nonsubtype selective agonist phenylephrine than to A61603. Chloroethylclonidine (50 muM for 10 min) did not affect contractile responses to A61603, but caused a significant inhibition of contractile responses to phenylephrine. In conclusion, it appears that alpha(1A)- and alpha(1D)-adrenoceptors play a role in adrenergic mediated contraction in the bovine tail artery.