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

Oxytocin stimulates phosphoinositide turnover in myometrium. To elucid ate whether the coupling mechanism involves the interaction of oxytoci n receptor with GTP-binding proteins, we examined oxytocin stimulation of guanosine triphosphatase (GTPase) activity and phospholipase-C act ivity in rat and human myometrial membranes. Oxytocin consistently sti mulated both GTPase and phospholipase-C activities, and both stimulati ons were attenuated by an antibody directed against the carboxyl-termi nals of the GTP-binding proteins, G alpha(q) and G alpha(11). Neutrali zation of the antibody by preincubation with antigenic peptide reverse d this inhibition. [Thr(4),Gly(7)]oxytocin, a specific oxytocin recept or agonist, stimulated both GTPase and phospholipase-C activities, and the stimulations were also inhibited by anti-G alpha(q/11) IgG. Immun oreactive GTP-binding proteins, G alpha(q) and G alpha(11), and phosph olipase-C beta(3) isoforms were present in myometrial membranes. These results indicate that stimulation of phospholipase-C activity by oxyt ocin in myometrium is mediated via G alpha(q), G alpha(11), or a close ly related GTP-binding protein, probably coupling to phospholipase-C b eta.