Carbachol-induced sensitivity changes in skeletal muscle and their mechanism of action.

Pretreatment of carbachol (in vitro), in various doses (5.5 pM to 550 nM), produced a significant decrease in the sensitivity of the frog rectus abdominis muscle to acetylcholine (ACh), in a dose-dependent manner. This action was observed with a 60 min incubation period. Contractions induced by potassium chloride (KCl) were unaffected by carbachol. Physostigmine (10 micrometer) potentiated the decrease in sensitivity induced by carbachol, whereas human plasma antagonised it. Low calcium (0.27 mM) in the medium and hexamethonium (300 micrometer) antagonised the sensitivity decrease induced by carbachol. These results suggest that carbachol decreases the sensitivity to ACh by releasing ACh from the presynaptic nerve terminals. The results further suggest that carbachol may release ACh by depolarising the presynaptic nicotinic receptors.