Inhibition by oxotremorine of acetylcholine resting release from guinea pig-ileum longitudinal muscle strips

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Abstract
Summary 1. Longitudinal muscle strips of the guinea-pig ileum were incubated in Tyrode solution containing either DFP or physostigmine as cholinesterase inhibior. After a 90 min preincubation period the acetylcholine resting release into the medium was determined. Acetylcholine was estimated by gas chromatography. 2. The resting release was 0.39 nmol/g×min irrespective of the cholinesterase inhibitor used. In the presence of hexamethonium, or after omission of external calcium, the resting release fell by 50 and 55%, respectively. 3. Oxotremorine (10−5 and 10−4 M) significantly inhibited the resting release of acetylcholine by 25 and 33%, respectively. The inhibitory effect of oxotremorine was completely reversed by atropine (3×10−7M). Oxotremorine did not reduce the spontaneous release of acetylcholine that occurred either in the presence of hexamethonium or in the absence of external calcium. 4. The acetylcholine content of the muscle strips was approximately doubled during the preincubation with a cholinesterase inhibitor. The subsequent incubation with oxotremorine did not lead to a further increase in the endogenous acetylcholine content. However, incubation of the muscle strips with oxotremorine in the absence of a cholinesterase inhibitor led to a rise in the endogenous acetylcholine concentration. Inin vivo experiments, oxotremorine also caused an increase in the acetylcholine content of the muscle strips. The possibility is discussed that the rise in the acetylcholine concentration following the administration of oxotremorine is a consequence of the decreased release. 5. It is concluded that oxotremorine inhibits the resting release of acetylcholine by activation of neuronal muscarinic receptors. The inhibitory effect of oxotremorine is linked to that fraction of the acetylcholine resting release that is calcium-dependent and that arises from propagated activity in cholinergic neurones. The results are consistent with the hypothesis of a feed-back control of acetylcholine release mediated by inhibitory muscarinic receptors.