Endocrinology, Vol 136, 1509-1515, Copyright © 1995 by Endocrine Society

ARTICLES

Oxytocin stimulates myometrial guanosine triphosphatase and phospholipase-C activities via coupling to G alpha q/11

CY Ku, A Qian, Y Wen, K Anwer and BM Sanborn
Department of Biochemistry and Molecular Biology, University of Texas Houston Medical School 77030.

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.

This article has been cited by other articles:

				M. Zhong, D. A. Murtazina, J. Phillips, C.-Y. Ku, and B. M. Sanborn Multiple Signals Regulate Phospholipase CBeta3 in Human Myometrial Cells Biol Reprod, June 1, 2008; 78(6): 1007 - 1017. [Abstract] [Full Text] [PDF]

				X.-B. Zhou, S. Lutz, F. Steffens, M. Korth, and T. Wieland Oxytocin Receptors Differentially Signal via Gq and Gi Proteins in Pregnant and Nonpregnant Rat Uterine Myocytes: Implications for Myometrial Contractility Mol. Endocrinol., March 1, 2007; 21(3): 740 - 752. [Abstract] [Full Text] [PDF]

				H. Thackare, H. D. Nicholson, and K. Whittington Oxytocin--its role in male reproduction and new potential therapeutic uses Hum. Reprod. Update, July 1, 2006; 12(4): 437 - 448. [Abstract] [Full Text] [PDF]

				C. Y. Ku, L. Babich, R. A. Word, M. Zhong, A. Ulloa, M. Monga, and B. M. Sanborn Expression of Transient Receptor Channel Proteins in Human Fundal Myometrium in Pregnancy Reproductive Sciences, April 1, 2006; 13(3): 217 - 225. [Abstract] [PDF]

				C.-Y. Ku, R. A. Word, and B. M. Sanborn Differential Expression of Protein Kinase A, AKAP 79, and PP2B in Pregnant Human Myometrial Membranes Prior to and During Labor Reproductive Sciences, September 1, 2005; 12(6): 421 - 427. [Abstract] [PDF]

				D. Devost, M. Girotti, M.-E. Carrier, C. Russo, and H. H. Zingg Oxytocin Induces Dephosphorylation of Eukaryotic Elongation Factor 2 in Human Myometrial Cells Endocrinology, May 1, 2005; 146(5): 2265 - 2270. [Abstract] [Full Text] [PDF]

				D. Y. Oh, J. A. Song, J. S. Moon, M. J. Moon, J. I. Kim, K. Kim, H. B. Kwon, and J. Y. Seong Membrane-Proximal Region of the Carboxyl Terminus of the Gonadotropin-Releasing Hormone Receptor (GnRHR) Confers Differential Signal Transduction between Mammalian and Nonmammalian GnRHRs Mol. Endocrinol., March 1, 2005; 19(3): 722 - 731. [Abstract] [Full Text] [PDF]

				A. Nicot, T. Otto, P. Brabet, and E. M. DiCicco-Bloom Altered Social Behavior in Pituitary Adenylate Cyclase-Activating Polypeptide Type I Receptor-Deficient Mice J. Neurosci., October 6, 2004; 24(40): 8786 - 8795. [Abstract] [Full Text] [PDF]

				A. Hasbi, D. Devost, S. A. Laporte, and H. H. Zingg Real-Time Detection of Interactions between the Human Oxytocin Receptor and G Protein-Coupled Receptor Kinase-2 Mol. Endocrinol., May 1, 2004; 18(5): 1277 - 1286. [Abstract] [Full Text] [PDF]

				L. G. Babich, C.-Y. Ku, H. W.J. Young, H. Huang, M. R. Blackburn, and B. M. Sanborn Expression of Capacitative Calcium TrpC Proteins in Rat MyometriumDuring Pregnancy Biol Reprod, April 1, 2004; 70(4): 919 - 924. [Abstract] [Full Text] [PDF]

				S. Mhaouty-Kodja, E. Houdeau, and C. Legrand Regulation of Myometrial Phospholipase C System and Uterine Contraction by {beta}-Adrenergic Receptors in Midpregnant Rat Biol Reprod, March 1, 2004; 70(3): 570 - 576. [Abstract] [Full Text] [PDF]

				E. K. Chien, L. Sweet, M. Phillippee, S. Marietti, T. T. Kim, D. A. Wolff, L. Thomas, and E. Bieber Protease-Activated Receptor Isoform Expression in Pregnant and Nonpregnant Rat Myometrial Tissue Reproductive Sciences, December 1, 2003; 10(8): 460 - 468. [Abstract] [PDF]

				M. Zhong, M. Yang, and B. M. Sanborn Extracellular Signal-Regulated Kinase 1/2 Activation by Myometrial Oxytocin Receptor Involves G{alpha}qG{beta}{gamma} and Epidermal Growth Factor Receptor Tyrosine Kinase Activation Endocrinology, July 1, 2003; 144(7): 2947 - 2956. [Abstract] [Full Text] [PDF]

				C.-Y. Ku and B. M. Sanborn Progesterone Prevents the Pregnancy-Related Decline in Protein Kinase A Association with Rat Myometrial Plasma Membrane and A-Kinase Anchoring Protein Biol Reprod, August 1, 2002; 67(2): 605 - 609. [Abstract] [Full Text] [PDF]

				M. Yang, W. Wang, M. Zhong, A. Philippi, O. Lichtarge, and B. M. Sanborn Lysine 270 in the Third Intracellular Domain of the Oxytocin Receptor is an Important Determinant for G{alpha}q Coupling Specificity Mol. Endocrinol., April 1, 2002; 16(4): 814 - 823. [Abstract] [Full Text] [PDF]

				S. Dogan, T. A. White, D. A. Deshpande, M. P. Murtaugh, T. F. Walseth, and M. S. Kannan Estrogen Increases CD38 Gene Expression and Leads to Differential Regulation of Adenosine Diphosphate (ADP)-Ribosyl Cyclase and Cyclic ADP-Ribose Hydrolase Activities in Rat Myometrium Biol Reprod, March 1, 2002; 66(3): 596 - 602. [Abstract] [Full Text] [PDF]

				M. Phillippe, M. Elovitz, and T. Saunders Thrombin-Stimulated Uterine Contractions in the Pregnant and Nonpregnant Rat Reproductive Sciences, September 1, 2001; 8(5): 260 - 265. [Abstract] [PDF]

				I. Boulven, B. Palmier, P. Robin, M. Vacher, S. Harbon, and D. Leiber Platelet-Derived Growth Factor Stimulates Phospholipase C-{gamma}1, Extracellular Signal-Regulated Kinase, and Arachidonic Acid Release in Rat Myometrial Cells: Contribution to Cyclic 3',5'-Adenosine Monophosphate Production and Effect on Cell Proliferation Biol Reprod, August 1, 2001; 65(2): 496 - 506. [Abstract] [Full Text] [PDF]

				B. F. Mitchell and B. Schmid Oxytocin and its Receptor in the Process of Parturition Reproductive Sciences, May 1, 2001; 8(3): 122 - 133. [Abstract] [PDF]

				B. Schmid, S. Wong, and B. F. Mitchell Transcriptional Regulation of Oxytocin Receptor by Interleukin-1{beta} and Interleukin-6 Endocrinology, April 1, 2001; 142(4): 1380 - 1385. [Abstract] [Full Text]

				G. Gimpl and F. Fahrenholz The Oxytocin Receptor System: Structure, Function, and Regulation Physiol Rev, April 1, 2001; 81(2): 629 - 683. [Abstract] [Full Text] [PDF]

				J. E. Mesonero, Z. Tanfin, M. Hilly, P. Colosetti, J.-P. Mauger, and S. Harbon Differential Expression of Inositol 1,4,5-Trisphosphate Receptor Types 1, 2, and 3 in Rat Myometrium and Endometrium During Gestation Biol Reprod, August 1, 2000; 63(2): 532 - 537. [Abstract] [Full Text]

				K. L. Dodge, D. W. Carr, C. Yue, and B. M. Sanborn A Role for AKAP (A Kinase Anchoring Protein) Scaffolding in the Loss of a Cyclic Adenosine 3',5'-Monophosphate Inhibitory Response in Late Pregnant Rat Myometrium Mol. Endocrinol., December 1, 1999; 13(12): 1977 - 1987. [Abstract] [Full Text]

				T. T. Kim, T. Saunders, E. Bieber, and M. Phillippe Tissue-Specific Protein Kinase C Isoform Expression in Rat Uterine Tissue Reproductive Sciences, November 1, 1999; 6(6): 293 - 300. [Abstract] [PDF]

				K. L. Dodge, D. W. Carr, and B. M. Sanborn Protein Kinase A Anchoring to the Myometrial Plasma Membrane Is Required for Cyclic Adenosine 3',5'-Monophosphate Regulation of Phosphatidylinositide Turnover Endocrinology, November 1, 1999; 140(11): 5165 - 5170. [Abstract] [Full Text]

				J. Ascher-Landsberg, T. Saunders, and M. Phillippe Tyrosine Kinase-Mediated Activation of Cytosolic Calcium Oscillations and Phastic Myometrical Contractions Reproductive Sciences, September 1, 1999; 6(5): 240 - 244. [Abstract] [PDF]

				B. Palmier, M. Vacher, S. Harbon, and D. Leiber A Tyrosine Kinase Signaling Pathway, Regulated by Calcium Entry and Dissociated from Tyrosine Phosphorylation of Phospholipase Cgamma -1, Is Involved in Inositol Phosphate Production by Activated G Protein-Coupled Receptors in Myometrium J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1022 - 1030. [Abstract] [Full Text]

				K. McKillen, S. Thornton, and C. W. Taylor Oxytocin increases the [Ca2+]i sensitivity of human myometrium during the falling phase of phasic contractions Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E345 - E351. [Abstract] [Full Text] [PDF]

				K. S. Lindeman, C. A. Hirshman, J. S. Kuhl, H. I. Levitsky, and C. W. Emala Chronic Oxytocin Pretreatment Inhibits Adenylyl Cyclase Activity in Cultured Rat Myometrial Cells Biol Reprod, November 1, 1998; 59(5): 1108 - 1115. [Abstract] [Full Text]

				S. Lajat, S. Harbon, and Z. Tanfin Carbachol-induced desensitization of PLC-beta pathway in rat myometrium: downregulation of Gqalpha /G11alpha Am J Physiol Cell Physiol, September 1, 1998; 275(3): C636 - C645. [Abstract] [Full Text] [PDF]

				M. Ushio-Fukai, K. K. Griendling, M. Akers, P. R. Lyons, and R. W. Alexander Temporal Dispersion of Activation of Phospholipase C-beta 1 and -gamma Isoforms by Angiotensin II in Vascular Smooth Muscle Cells. ROLE OF alpha q/11, alpha 12, AND beta gamma G PROTEIN SUBUNITS J. Biol. Chem., July 31, 1998; 273(31): 19772 - 19777. [Abstract] [Full Text] [PDF]

				M. Phillippe and E. K. Chien Intracellular Signaling and Phasic Myometrial Contractions Reproductive Sciences, July 1, 1998; 5(4): 169 - 177. [Abstract] [PDF]

				K. L. Dodge and B. M. Sanborn Evidence for Inhibition by Protein Kinase A of Receptor/G{alpha}q/Phospholipase C (PLC) Coupling by a Mechanism Not Involving PLC{beta}2 Endocrinology, May 1, 1998; 139(5): 2265 - 2271. [Abstract] [Full Text] [PDF]

				C. M. Harris, T. Saunders, D. A. Baunoch, and M. Phillippe Gq-Protein Alpha Subunit Expression and Distribution in Pregnant Rat Myometrial Tissues Reproductive Sciences, July 1, 1997; 4(4): 209 - 217. [Abstract] [PDF]

				M. Phillippe and A. Basa Effects of Sodium and Calcium Channel Blockade on Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Tissue Reproductive Sciences, March 1, 1997; 4(2): 72 - 77. [Abstract] [PDF]

				R. Postina, E. Kojro, and F. Fahrenholz Separate Agonist and Peptide Antagonist Binding Sites of the Oxytocin Receptor Defined by Their Transfer into the V2 Vasopressin Receptor J. Biol. Chem., December 6, 1996; 271(49): 31593 - 31601. [Abstract] [Full Text] [PDF]

				C. Yue, C.-Y. Ku, M. Liu, M. I. Simon, and B. M. Sanborn Molecular Mechanism of the Inhibition of Phospholipase C beta 3 by Protein Kinase C J. Biol. Chem., September 22, 2000; 275(39): 30220 - 30225. [Abstract] [Full Text] [PDF]