title: Regulation of LPA receptor function by estrogens.
abstract: 17beta-Estradiol induced LPA(1) receptor desensitization in C9 cells stably expressing LPA(1) receptors and transiently expressing estrogen receptor alpha. Such desensitization was evidenced by a reduction in lysophosphatidic acid-mediated Ca(2+)mobilization and it was associated to receptor phosphorylation and internalization. These effects of 17beta-estradiol were rapid (taking place over 5 min) and were blocked by the estrogen receptor antagonist ICI 182780. Similarly, inhibitors of phosphoinositide 3-kinase (wortmannin and LY294002) and of protein kinase C (staurosporine and Gö 6976) blocked 17beta-estradiol-induced LPA(1) receptor desensitization and phosphorylation. Confocal microscopy evidenced LPA(1) receptor internalization in response to 17beta-estradiol treatment. Association between LPA(1) receptors and protein kinase C alpha was suggested by co-immunoprecipitation assays. Protein kinase C alpha was associated with LPA(1) receptors in the absence of stimulus and such association further increased in a dynamic fashion in response to 17beta-estradiol. The results demonstrated that in C9 cells estrogens modulate LPA(1) action through estrogen receptor alpha with the participation of protein kinase C alpha and phosphoinositide 3-kinase.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, México, D. F. 04510. México.
authors.forename: Aliesha
authors.initials: A
authors.lastname: González-Arenas
authors.forename: S Eréndira
authors.initials: SE
authors.lastname: Avendaño-Vázquez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabrera-Wrooman
authors.forename: Diana
authors.initials: D
authors.lastname: Tapia-Carrillo
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Becerra
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects; D014162:Transfection
chemical_list: D004958:Estradiol; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D049368:Receptors, Lysophosphatidic Acid; D011993:Recombinant Fusion Proteins; C506487:ESR1 protein, human; C032881:lysophosphatidic acid