کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2028613 1070430 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Progesterone metabolites rapidly stimulate calcium influx in human platelets by a src-dependent pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Progesterone metabolites rapidly stimulate calcium influx in human platelets by a src-dependent pathway
چکیده انگلیسی

The effects of several steroids and their metabolites were examined for their ability to rapidly alter intracellular free calcium ([Ca2+]i) in the anucleate human platelet. Earlier studies suggested that steroids had direct and rapid non-genomic effects to alter platelet physiology. The rationale for performing this study was to investigate the signal transduction events being activated by steroids. Super-physiologic concentrations (1.0–10.0 μM) of β-estradiol and several estradiol metabolites and analogs potentiated (approximately twofold) the action of thrombin to elevate [Ca2+]i in platelets, whereas 10.0 μM progesterone inhibited the action of thrombin by 10–15%. Progesterone and β-estradiol by themselves did not affect [Ca2+]i. Progesterone metabolites can achieve high blood concentrations. Some progesterone metabolites, particularly those in the β-conformation, were potent stimulators of Ca2+ influx and intracellular Ca2+ mobilization in platelets. They activated phospholipase C because their ability to increase [Ca2+]i was inhibited by the phospholipase C inhibitor U-73122. The ability of pregnanediol and collagen to increase [Ca2+]i was inhibited by the src tyrosine kinase inhibitor PP1, whereas the actions of thrombin and thapsigargin to increase [Ca2+]i were not affected by PP1. The effects of progesterone metabolites to increase [Ca2+]i were observed with concentrations as low as 0.1 μM. Pregnanolone synergized with thrombin to increase [Ca2+]i. It is hypothesized that human platelets possess receptors for progesterone metabolites. These receptors when stimulated will activate platelets by causing a rapid increase in [Ca2+]i. Pregnanolone, isopregnanediol and pregnanediol were the most effective stimulators of this newly identified src-dependent signal transduction system in platelets. Progesterone metabolites may regulate platelet aggregation and hence thrombosis in vivo.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 73, Issue 7, August 2008, Pages 738–750
نویسندگان
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