17β-estradiol elevates cGMP and, via plasma membrane recruitment of protein kinase GIa, stimulates Ca2+ efflux from rat hepatocytes

Stratton, Rebecca C. and Squires, Paul E. and Green, Anne K. (2010) 17β-estradiol elevates cGMP and, via plasma membrane recruitment of protein kinase GIa, stimulates Ca2+ efflux from rat hepatocytes. Journal of Biological Chemistry, 28 (35). pp. 27201-27212. ISSN 0021-9258

Full content URL: http://dx.doi.org/10.1074/jbc.M110.103630

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Abstract

Rapid non-genomic effects of 17 beta-estradiol, the principal circulating estrogen, have been observed in a wide variety of cell types. Here we investigate rapid signaling effects of 17 beta-estradiol in rat hepatocytes. We show that, above a threshold concentration of 1 nM, 17 beta-estradiol, but not 17 alpha-estradiol, stimulates particulate guanylyl cyclase to elevate cGMP, which through activation and plasma membrane recruitment of protein kinase G isoform I alpha, stimulates plasma membrane Ca2+-ATPase-mediated Ca2+ efflux from rat hepatocytes. These effects are extremely rapid in onset and are mimicked by a membrane-impermeant 17 beta-estradiol-BSA conjugate, suggesting that 17 beta-estradiol acts at the extracellular face of the plasma membrane. We also show that 17 beta-estradiol binds specifically to the intact hepatocyte plasma membrane through an interaction that is competed by an excess of atrial natriuretic peptide but also shows many similarities to the pharmacological characteristics of the putative gamma-adrenergic receptor. We, therefore, propose that the observed rapid signaling effects of 17 beta-estradiol are mediated either through the guanylyl cyclase A receptor for atrial natriuretic peptide or through the gamma-adrenergic receptor, which is either itself a transmembrane guanylyl cyclase or activates a transmembrane guanylyl cyclase through cross-talk signaling.

Keywords:Protein kinase
Subjects:Library of Congress Subject Areas > Q Science > QD Chemistry
Divisions:College of Science > School of Life Sciences
ID Code:14067
Deposited On:20 Apr 2011 10:52

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