Modulation of cytosolic protein kinase C and calcium ion activity by steroid hormones in rat distal colon

被引:106
作者
Doolan, CM
Harvey, BJ
机构
[1] Wellcome Trust Cell. Physiol. R., Department of Physiology, University College, Cork
基金
英国惠康基金;
关键词
D O I
10.1074/jbc.271.15.8763
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Studies from our laboratory have demonstrated rapid (< 1 min) non-genomic activation of Na+-H+ exchange and potassium recycling by mineralocorticoids in human and rat colonic epithelium. It has previously been demonstrated that Na+-H+ exchange may be stimulated by protein kinase C (PKC) activation; therefore, we examined the effect of mineralocorticoids on PKC activity in rat colonic epithelium, Activation (after 15 min of incubation) of basal PKC activity was observed in cytosolic fractions of rat colonic epithelium by aldosterone, fludrocortisone, and deoxycorticosterone acetate, In all instances, PKC activation was inhibited by the PKC inhibitor bisindolylmaleimide (GF109203X), Hydrocortisone failed to activate PKC activity. Stimulation of basal intracellular free calcium [Ca2+](i) was observed, in isolated rat colonic crypts, following aldosterone addition. This stimulatory effect was inhibited by the PKC inhibitor, chelerythrine chloride. Hydrocortisone failed to increase [Ca2+](i), These results indicate that intracellular signaling for aldosterone involves changes in [Ca2+](i) via activation of PKC, Since the stimulation of PKC and increase in [Ca2+](i) are apparent at normal circulating levels of aldosterone, our findings have major implications for the reassessment of mineralocorticoid effects on electrolyte homeostasis.
引用
收藏
页码:8763 / 8767
页数:5
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