Estrogens cross-talk to alpha1b-adrenergic receptors.
beta-Estradiol induced alpha1b-adrenergic receptor desensitization in U373 MG cells stably expressing alpha1b-adrenoceptors, as evidenced by a reduction in the adrenergic-mediated Ca2+ mobilization; desensitization was associated with receptor phosphorylation and internalization. These effects of beta-estradiol were rapid (taking place during 15 min) and were blocked by the estrogen receptor antagonist ICI 182,780 (faslodex). Likewise, inhibitors of phosphoinositide 3-kinase [wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)] and of protein kinase C [staurosporine, 3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl) maleimide (Ro31-8220), and rottlerin] blocked the desensitization and phosphorylation of alpha1b-adrenoceptors induced by estradiol. The formation of a complex was suggested by coimmunoprecipitation assays. The regulatory and catalytic subunits of phosphoinositide 3-kinase (p85 and p110) and protein kinase C delta were associated with alpha1b-adrenoceptors in the absence of stimulus, and such association further increased in a dynamic fashion in response to beta-estradiol. In cells cotransfected with the estrogen receptor alpha and alpha1b-adrenoceptors, beta-estradiol induced phosphorylation, desensitization and internalization of the adrenergic receptors; pretreatment with ICI 182,780 inhibited these effects. Our data support the idea that estrogens modulate alpha1b-adrenergic action through estrogen receptor alpha.
González-Arenas
Aliesha
A
Instituto de Fisiología Celular, UNAM, Ap. postal 70-248, México D. F. 04510.
Aguilar-Maldonado
Beatriz
B
Avendaño-Vázquez
S Eréndira
SE
García-Sáinz
J Adolfo
JA
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D004705:Endocytosis / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D006801:Humans; D018613:Microscopy, Confocal; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000187:drug effects; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D002118:Calcium; D004958:Estradiol; D047628:Estrogen Receptor alpha; D004967:Estrogens; D000077267:Fulvestrant; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051745:Protein Kinase C-delta; D018340:Receptors, Adrenergic, alpha-1; D019311:Staurosporine; D000077191:Wortmannin; C547716:ADRA1B protein, human