Carbachol but Not Acetylcholine Inhibits Contraction by the Protein Kinase C-Dependent and -Independent Pathways in the Smooth Muscle of Guinea Pig Taenia Caeci

Abstract

In the intestinal smooth muscle of guinea pig taenia caeci, acetylcholine and carbachol induced a transient contraction followed by a sustained contraction. The magnitudes of the transient and sustained contractions were similar when muscle was stimulated with acetylcholine (0.1 μM – 1 mM) or a lower concentration (0.1 μM) of carbachol. However, higher concentrations of carbachol (1–100 μM) induced significantly smaller sustained contraction than the transient contraction. In the 45 mM KCl-stimulated strips, addition of 100 μM carbachol induced a transient increase followed by a sustained decrease in the contractile tension. In contrast, acetylcholine (0.1 μM – 1 mM) showed only weak inhibitory effects on the high K+-induced contraction either in the absence or presence of a cholinesterase inhibitor, 0.5 αM diisopropylfluorophosphate. The same concentration of diisopropylfluorophosphate shifted the concentration-response curve for acetylcholine to lower concentrations. In the muscles pretreated with 3 μM phorbol 12-myristate 13-acetate for 24 hr to desensitize protein kinase C, sustained contractions induced by higher concentrations of carbachol (1-100 μM) were significantly greater than those in the strips without the treatment with phorbol ester. However, the transient contraction and the contraction induced by a lower concentration (0.1 μM) of carbachol were not changed by the treatment with phorbol ester. Pretreatment with phorbol ester attenuated the inhibitory effect of carbachol on the high K+-induced contraction. These results suggest that the inhibitory effects of carbachol is composed of two phases: protein kinase C-independent transient inhibition and protein kinase C-dependent sustained inhibition.