NORADRENALINE-MEDIATED CONTRACTIONS OF OVINE UTERINE ARTERY - ROLE OFINOSITOL 1,4,5-TRISPHOSPHATE

To elucidate the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) as a second messenger through which noradrenaline regulates contractio ns of the uterine artery, we present here studies designed to characte rize simultaneously the noradrenaline-mediated contractions and Ins(1, 4,5)P-3 formation in isolated uterine arteries from near-term pregnant sheep. Noradrenaline stimulated a rapid increase of Ins(1,4,5)P-3 for mation with the peak at 30 second. Simultaneous measurement of noradre naline-induced contractile responses and Ins(1,4,5)P-3 formation revea led a significant linear correlation between these two events. In acco rdance with the contractile results, the noradrenaline-mediated inosit ol phosphate accumulation was blocked by prazosin (0.1 mu M), but not by yohimbine (0.1 mu M). Pre-treatment of tissues with pertussis toxin (200 ng/ml, 3 h) failed to block noradrenaline-induced inositol phosp hate accumulation. We conclude that, in the uterine artery of late pre gnancy, the alpha(1)-adrenoceptor-elicited contraction, at least the i nitial phasic component, is predominantly mediated by the formation of Ins(1,4,5)P-3, leading to release of Ca2+ from intracellular stores.