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. [Thr4,Gly7]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.
Ku
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Department of Biochemistry and Molecular Biology, University of Texas Houston Medical School 77030.
Qian
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Wen
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Anwer
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Sanborn
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BM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D009215:Myometrium / Q000201:enzymology*; D010121:Oxytocin / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D018045:Receptors, Oxytocin / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
D000906:Antibodies; D007074:Immunoglobulin G; D018045:Receptors, Oxytocin; D010121:Oxytocin; C045427:oxytocin, Thr(4)-Gly(7)-; D010738:Type C Phospholipases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins