POTASSIUM CHANNEL STIMULATION BY NATRIURETIC PEPTIDES THROUGH CGMP-DEPENDENT DEPHOSPHORYLATION

被引:239
作者
WHITE, RE
LEE, AB
SHCHERBATKO, AD
LINCOLN, TM
SCHONBRUNN, A
ARMSTRONG, DL
机构
[1] NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA
[2] UNIV ALABAMA, DEPT PATHOL, BIRMINGHAM, AL 35294 USA
[3] UNIV TEXAS, SCH MED, DEPT PHARMACOL, HOUSTON, TX 77225 USA
关键词
D O I
10.1038/361263a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
NATRIURETIC peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMp)1,2, but the mechanism of cGMP action is unclear3. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP4,5; however, this mechanism is not involved in the action of cGMP on other channels6 or on Ca2+ channels in other cells7,8. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium9,10. In an electrophysiological study on rat pituitary tumour cells11, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems12.
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页码:263 / 266
页数:4
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