Heterogeneity and complexity of α 1-adrenoceptors in the ovine uterine artery and umbilical vein

Abstract

To understand the subtypes of α 1-adrenoceptors in the regulation of uterine and umbilical vascular function, the subtypes of α 1-adrenoceptors in the ovine uterine artery and umbilical vein were investigated pharmacologically. The use of the irreversible α 1B-adrenoceptor antagonist, chloroethylclonidine, revealed the heterogeneity of α 1-adrenoceptors in these two tissues. Chloroethylclonidine showed different patterns of action. While it depressed the maximal contraction to norepinephrine in the umbilical vein, it did not decrease the maximal response in the uterine artery. The α 1A-adrenoceptor antagonist, 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (WB 4101), competitively inhibited norepinephrine-induced contractile responses in the ovine uterine artery and umbilical vein with intermediate pA 2 values of 8.30 and 8.45, respectively. Combined use of chloroethylclonidine with either prazosin or WB 4101 produced an additive inhibition of norepinephrine-induced contractions in both tissues, suggesting an interaction of WB 4101 with a chloroethylclonidine-insensitive α 1-adrenoceptor. However, the chloroethylclonidine-insensitive α 1-adrenoceptor differed on the affinity for prazosin in the uterine artery and umbilical vein. The Ca 2+ channel blocker, nifedipine, inhibited contractions to both the chloroethylclonidine-sensitive α 1-adrenoceptor (α 1B subtype) and the chloroethylclonidine-insensitive α 1-adrenoceptor in both tissues. Prazosin, WB 4101 and chloroethylclonidine all inhibited norepinephrine-induced contraction due to the release of calcium from intracellular stores in both tissues. Our results suggest that there is heterogeneity and complexity of α 1-adrenoceptors in the ovine uterine artery and umbilical vein. Both the chloroethylclonidine-sensitive and -insensitive α 1-adrenoceptor may use both intracellular and extracellular Ca 2+ sources. © 1997 Elsevier Science B.V. All rights reserved.