Role of phospholipase C-δ1 in oxytocin receptor signaling: Evidence for an effector

Abstract

Although the oxytocin receptor modulates intracellular calcium levels in inyometriuin, the identities of signal molecules have not been clearly clarified. Our previous studies on oxytocin receptor signaling demonstrated that 80 kl)a Gah is a signal mediator (Baek et al.. 1996. Biochemical J. 315, 739744). To elucidate the effector in oxytocin receptor signaling, we evaluated oxytocin-mediated activation of phospholipase 0 (PLC) by using the solubilized membranes from human myometrium and a three components preparations containing oxytocin receptor/Go/,/PLC-<51 complex. PLC-61 activity in the three components preparations, as well as PLC activity in solubilized membranes increased by oxytocin in the presence of calcium and activated Go/, (GTP bound Go-4). Furthermore, stimulated PLC and -61 activity resulting from activation of Go/, via oxytocin receptor were significantly attenuated by the selective oxytocin antagonist, desGly-NH2d(CH2)5[Tyr(Me)2,Thr4]OVT or GDP. Consistent with these observations, in co-immunoprecipitation and co imrnunoadsorption of PLC-iU in three components preparations by anti-Go;,7 antibody, the PLC-M tightly coupled to activated Ga/i by stimulation of oxytocin receptor. These results indicate that PLC-M is an effector of Gn/jmediated oxytocin receptor signaling.