Effect of ketamine on cholinergic transmission in the isolated guinea-pig ileum preparation

The effect of ketamine on cholinergic transmission in the isolated guinea-pig ileum was studied. Low concentrations of ketamine (less than 4.2 microM) produced slight augmentation of nicotine, and carbachol-induced, as well as electrically evoked contractions. Higher concentrations caused concentration-dependent inhibition of the contractions produced by all three interventions. Ketamine inhibition of nicotine-induced contractions was found to be relatively independent of external Ca2+-ion concentration. Results obtained suggest that low concentrations of ketamine facilitate, while higher concentrations inhibit cholinergic transmission, by an action exerted on postganglionic parasympathetic nerve terminals, although effects of the compound on parasympathetic ganglia cannot be excluded. Evidence was also obtained for a direct postjunctional inhibitory action by ketamine.