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Am J Physiol Gastrointest Liver Physiol 262: G118-G122, 1992;
0193-1857/92 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 1 118-G122, Copyright © 1992 by American Physiological Society

ARTICLES

An inhibitor of Ca2+/calmodulin-dependent protein kinase II, KN-62, inhibits cholinergic-stimulated parietal cell secretion

Y. Tsunoda, M. Funasaka, I. M. Modlin, H. Hidaka, L. M. Fox and J. R. Goldenring
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.

Cholinergic stimulation of parietal cell secretion is mediated by an increase in intracellular calcium. KN-62, a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK II), has recently been synthesized (Tokomitsu et al. J. Biol. Chem. 265: 4315-4320, 1990). To define the role of CaMK II in parietal cell secretion, we determined the effects of KN-62 on secretagogue-stimulated acid secretion in isolated rabbit parietal cells. Pretreatment of parietal cells with KN-62 resulted in the inhibition of carbachol-stimulated [14C]aminopyrine uptake over a concentration range of 3 to 60 microM (IC50 of 20 microM). KN-62 (60 microM) reduced carbachol-stimulated aminopyrine uptake to unstimulated levels. KN-62 did not alter carbachol-stimulated increases in cytoplasmic free Ca2+ concentration. High concentrations of KN-62 (60 microM) elicited a small decrease in aminopyrine uptake stimulated by forskolin, but did not significantly inhibit histamine stimulation. A potent CaMK II activity was identified in total membrane from parietal cells. These results suggest that CaMK II may mediate cholinergic-stimulated parietal cell secretion.


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