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Insulin-like growth factor-I inhibits rat arterial K-ATP channels through PI 3-kinase.

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posted on 2008-10-06, 14:36 authored by Y. Hayabuchi, Gary B. Willars, N. B. Standen, N. W. Davies
Since, in addition to its growth-promoting actions, insulin-like growth factor-I (IGF-I) has rapid vasoactive actions, we investigated the effects of IGF-I on whole-cell ATP-sensitive K+ (K-ATP) currents of rat mesenteric arterial smooth muscle cells. IGF-I (10 or 30 nM) reduced K-ATP currents activated by pinacidil or a membrane permeant cAMP analogue. Inhibition of phospholipase C, protein kinase C, protein kinase A, mitogen-activated protein kinase or mammalian target of rapamycin (mTOR) did not prevent the action of IGF-I. However, inhibition of K-ATP currents by IGF-I was abolished by the tyrosine kinase inhibitor genistein or the phosphoinositide 3-kinase inhibitors, LY 294002 and wortmannin. Intracellular application of either phosphatidylinositol 4,5-bisphosphate (PIP-2) or phosphatidylinositol 3,4,5-trisphosphate (PIP-3) increased the K-ATP current activated by pinacidil and abolished the inhibitory effect of IGF-I. Thus, we show regulation of arterial K-ATP channels by polyphosphoinositides and report for the first time that IGF-I inhibits these channels via a phosphoinositide 3-kinase-dependent pathway.

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Citation

Biochemical and Biophysical Research Communications, 2008, 374 (4), pp. 742-746.

Published in

Biochemical and Biophysical Research Communications

Publisher

Elsevier

issn

0006-291X

Copyright date

2008

Available date

2008-10-06

Publisher version

http://www.sciencedirect.com/science/article/pii/S0006291X08014484

Language

en

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