17 beta-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 17 beta-estradiol were rapid (taking place over 5 min) and were blocked by the estrogen receptor antagonist 10 182780. Similarly, inhibitors of phosphoinositide 3-kinase (wortmannin and LY294002) and of protein kinase C (staurosporine and Go 6976) blocked 17 beta-estradiol-induced LPA(1) receptor desensitization and phosphorylation. Confocal microscopy evidenced LPA(1) receptor internalization in response to 17 beta-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 17 beta-estradiol. The results demonstrated that in C9 cells estrogens modulate LPA(1) action through estrogen receptor a with the participation of protein kinase C alpha and phosphoinositide 3-kinase. (C) 2007 Elsevier B.V. All rights reserved.
Última actualización: 15/12/2017