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Article
Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation
Nature
  • Richard E. White, Philadelphia College of Osteopathic Medicine
  • A. B. Lee
  • A. D. Shcherbatko
  • T. M. Lincoln
  • A. Schonbrunn
  • D. L. Armstrong
Document Type
Article
Publication Date
1-1-1993
Disciplines
Abstract
NATRIRETIC 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 cells, 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.
Comments

This article was published in Nature, Volume 361, Issue 6409, Pages 263-266.

The published version is available at http://dx.doi.org/10.1038/361263a0 .

Copyright © 1993 NPG.

Citation Information
Richard E. White, A. B. Lee, A. D. Shcherbatko, T. M. Lincoln, et al.. "Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation" Nature Vol. 361 Iss. 6409 (1993) p. 263 - 266
Available at: http://works.bepress.com/richard_white/35/