OXYTOCIN STIMULATES MYOMETRIAL GUANOSINE TRIPHOSPHATASE AND PHOSPHOLIPASE-C ACTIVITIES VIA COUPLING TO G-ALPHA(Q/11)

Oxytocin stimulates phosphoinositide turnover in myometrium. To elucidate whether the coupling mechanism involves the interaction of oxytocin receptor with GTP-binding proteins, we examined oxytocin stimulation of guanosine triphosphatase (GTPase) activity and phospholipase-C activity in rat and human myometrial membranes. Oxytocin consistently stimulated both GTPase and phospholipase-C activities, and both stimulations were attenuated by an antibody directed against the carboxyl-terminals of the GTP-binding proteins, G alpha(q) and G alpha(11). Neutralization of the antibody by preincubation with antigenic peptide reversed this inhibition. [Thr(4),Gly(7)]oxytocin, a specific oxytocin receptor agonist, stimulated both GTPase and phospholipase-C activities, and the stimulations were also inhibited by anti-G alpha(q/11) IgG. Immunoreactive GTP-binding proteins, G alpha(q) and G alpha(11), and phospholipase-C beta(3) isoforms were present in myometrial membranes. These results indicate that stimulation of phospholipase-C activity by oxytocin in myometrium is mediated via G alpha(q), G alpha(11), or a closely related GTP-binding protein, probably coupling to phospholipase-C beta.