title: Phospholipase C-delta1 and oxytocin receptor signalling: evidence of its role as an effector.
abstract: Although the oxytocin receptor modulates intracellular Ca2+ ion levels in myometrium, the identities of signal molecules have not been clearly clarified. Our previous studies on oxytocin receptor signalling demonstrated that 80 kDa Ghalpha is a signal mediator [Baek, Kwon, Lee, Kim, Muralidhar and Im (1996) Biochem. J. 315, 739-744]. To elucidate the effector in the oxytocin receptor signalling pathway, we evaluated the oxytocin-mediated activation of phospholipase C (PLC) by using solubilized membranes from human myometrium and a three-component preparation containing the oxytocin receptor-Ghalpha-PLC-delta1 complex. PLC-delta1 activity in the three-component preparation, as well as PLC activity in solubilized membranes, was increased by oxytocin in the presence of Ca2+ and activated Ghalpha (GTP-bound Ghalpha). Furthermore the stimulated PLC-delta1 activity resulting from activation of Ghalpha via the oxytocin receptor was significantly attenuated by the selective oxytocin antagonist desGly-NH2d(CH2)5[Tyr(Me)2,Thr4]ornithine vasotocin or GDP. Consistent with these observations, co-immunoprecipitation and co-immunoadsorption of PLC-delta1 in the three-component preparation by anti-Gh7alpha antibody resulted in the PLC-delta1 being tightly coupled to activated Ghalpha on stimulation of the oxytocin receptor. These results indicate that PLC-delta1 is the effector for Ghalpha-mediated oxytocin receptor signalling.
authors.affiliation: Department of Biochemistry, College of Medicine, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Gu, Seoul 156-756, South Korea.
authors.forename: E S
authors.initials: ES
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Won
authors.forename: K J
authors.initials: KJ
authors.lastname: Han
authors.forename: P G
authors.initials: PG
authors.lastname: Suh
authors.forename: S H
authors.initials: SH
authors.lastname: Ryu
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: H Y
authors.initials: HY
authors.lastname: Yun
authors.forename: N S
authors.initials: NS
authors.lastname: Kwon
authors.forename: K J
authors.initials: KJ
authors.lastname: Baek
mesh_terms: D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D054803:Phospholipase C delta; D018045:Receptors, Oxytocin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D018045:Receptors, Oxytocin; D010121:Oxytocin; D010738:Type C Phospholipases; C518024:PLCD1 protein, human; D054803:Phospholipase C delta; D002118:Calcium