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

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.