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17 -Estradiol elevates cGMP and, via plasma membrane recruitment of protein kinase GI , stimulates Ca2+ efflux from rat hepatocytes
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Stratton, R. C., Squires, P. E. and Green, Anne K.. (2010) 17 -Estradiol elevates cGMP and, via plasma membrane recruitment of protein kinase GI , stimulates Ca2+ efflux from rat hepatocytes. Journal of Biological Chemistry, Vol.285 (No.35). pp. 27201-27212. ISSN 0021-9258
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Official URL: http://dx.doi.org/10.1074/jbc.M110.103630
Abstract
Rapid non-genomic effects of 17β-estradiol, the principal circulating estrogen, have been observed in a wide variety of cell types. Here we investigate rapid signaling effects of 17β-estradiol in rat hepatocytes. We show that, above a threshold concentration of 1 nM, 17β-estradiol, but not 17α-estradiol, stimulates particulate guanylyl cyclase to elevate cGMP, which through activation and plasma membrane recruitment of protein kinase G isoform Iα, 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 17β-estradiol-BSA conjugate, suggesting that 17β-estradiol acts at the extracellular face of the plasma membrane. We also show that 17β-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 γ-adrenergic receptor. We, therefore, propose that the observed rapid signaling effects of 17β-estradiol are mediated either through the guanylyl cyclase A receptor for atrial natriuretic peptide or through the γ-adrenergic receptor, which is either itself a transmembrane guanylyl cyclase or activates a transmembrane guanylyl cyclase through cross-talk signaling.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Warwick Medical School > Education Development and Research Faculty of Medicine > Warwick Medical School |
| Journal or Publication Title: | Journal of Biological Chemistry |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| ISSN: | 0021-9258 |
| Date: | 2010 |
| Volume: | Vol.285 |
| Number: | No.35 |
| Page Range: | pp. 27201-27212 |
| Identification Number: | 10.1074/jbc.M110.103630 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | http://wrap.warwick.ac.uk/id/eprint/45060 |
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