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Am J Physiol Cell Physiol 258: C787-C793, 1990;
0363-6143/90 $5.00
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AJP - Cell Physiology, Vol 258, Issue 5 C787-C793, Copyright © 1990 by American Physiological Society


ARTICLES

Dual effects of carbachol on cytosolic Ca2+ and contraction in intestinal smooth muscle

M. Mitsui and H. Karaki
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.

The effects of carbachol on muscle tension and cytosolic Ca2+ concentrations ([Ca2+]cyt), measured with fura-2, were examined in the guinea pig intestinal smooth muscle. Carbachol induced an initial transient increase followed by a sustained increase in [Ca2+]cyt and muscle tension. Higher concentrations of carbachol induced larger transient changes and smaller sustained changes. In the presence of carbachol, application of Ca2+ to a Ca2(+)-depleted muscle induced a contraction that was smaller in the presence of higher concentrations of carbachol. High concentrations of carbachol inhibited the high-K(+)-stimulated muscle tension and [Ca2+]cyt. Contractile and inhibitory effects of carbachol were inhibited by a muscarinic M2 antagonist. Increase in the external Ca2+ concentration or addition of BAY K 8644, a Ca2(+)-channel activator, antagonized the inhibitory effect. There was a linear correlation between log [Ca2+]cyt and muscle tension under the conditions employed in the present experiments (r = 0.949). These results suggest that lower concentrations of carbachol increase [Ca2+]cyt and induce contraction, whereas high concentrations of carbachol have an additional effect to decrease [Ca2+]cyt and inhibit contraction by a Ca2(+)-channel blocker-like action.


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