inositol-1-4-5-trisphosphate and Whooping-Cough

To elucidate the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) as a second messenger through which noradrenaline regulates contractions of the uterine artery, we present here studies designed to characterize simultaneously the noradrenaline-mediated contractions and Ins(1,4,5)P3 formation in isolated uterine arteries from near-term pregnant sheep. Noradrenaline stimulated a rapid increase of Ins(1,4,5)P3 formation with the peak at 30 second. Simultaneous measurement of noradrenaline-induced contractile responses and Ins(1,4,5)P3 formation revealed a significant linear correlation between these two events. In accordance with the contractile results, the noradrenaline-mediated inositol phosphate accumulation was blocked by prazosin (0.1 microM), but not by yohimbine (0.1 microM). Pre-treatment of tissues with pertussis toxin (200 ng/ml, 3 h) failed to block noradrenaline-induced inositol phosphate accumulation. We conclude that, in the uterine artery of late pregnancy, the alpha 1-adrenoceptor-elicited contraction, at least the initial phasic component, is predominantly mediated by the formation of Ins(1,4,5)P3, leading to release of Ca2+ from intracellular stores.

Topics: Animals; Arteries; Dose-Response Relationship, Drug; Female; Inositol 1,4,5-Trisphosphate; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Prazosin; Sheep; Uterus; Whooping Cough