Noradrenaline-mediated contractions of ovine uterine artery: role of inositol 1,4,5-trisphosphate.
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.
Zhang
L
L
Department of Pharmacology, Loma Linda University School of Medicine, CA 92350, USA.
Pearce
W J
WJ
Longo
L D
LD
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D012756:Sheep; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects; D014917:Whooping Cough
D015544:Inositol 1,4,5-Trisphosphate; D009638:Norepinephrine; D011224:Prazosin