Effects of atropine on responses to directly and indirectly acting cholinomimetics

Abstract

In the isolated guinea-pig ileum atropine delayed the onset and slowed the rate of contraction of responses to indirectly acting cholinomimetics (nicotine, dimethylphenylpipezinium, dimethlaminoethanol, dimethylaminopropanol and supinidine), while response heights were little affected. In contrast, atropine had little effect on the time taken for acetylcholine to produce its peak response, while contraction height was reduced. The competitive action of atropine on concentration-effect curves to acetycholine was not apparent with indirectly acting cholinomimetics. Nevertheless analysis of time-effect rather than concentration-effect curves showed that atropine competitively antagonized responses to acetylcholine released by the latter agonists. Atropine antagonism of exogenously administered and endogenously released acetylcholine was similar. The extent and offset of acetylcholine antagonism by atropine was unaffected by indirectly acting compounds. With indirectly acting cholinomimetics, the atropine resistance may be explained on the basis of the differing mechanisms by which exogenous and endogenous acetylcholine elicit responses, rather than a difference in the receptors involved or limited access of atropine to endogenous sites.