Muscarinic presynaptic inhibition of synaptic transmission in myenteric plexus of guinea-pig ileum.

1. The effect of oxotremorine (300 pM to 30 nM) on synaptic transmission in isolated myenteric ganglia of guinea-pig ileum was investigated with intracellular recording techniques. 2. These low concentrations of oxotremorine had no effect on the resting membrane potentials or on the membrane conductance. 3. Oxotremorine reduced the amplitude of the fast excitatory post-synaptic potential (e.p.s.p.) but did not reduce the amplitude of nicotinic responses to ionophoretic application of acetylcholine (ACh). This effect of oxotremorine on the fast e.p.s.p. was dose-dependent; the amplitude was reduced by about 45% by 30 nM-oxotremorine. 4. Non-cholinergic slow e.p.s.p.s evoked by repetitive presynaptic nerve stimulation were reduced in amplitude by oxotremorine. 5. Hyoscine or atropine (1 nM) completely antagonized both these effects of oxotremorine (30 nM). 6. Muscarinic antagonists alone increased the amplitude of second and subsequent fast e.p.s.p.s when these were evoked at intervals of 1 s, and increased the amplitude and duration of the slow e.p.s.p. evoked by repetitive presynaptic nerve stimulation. 7. The results indicate that muscarinic receptor activation inhibits the release of the transmitters which mediate both the fast and the slow e.p.s.p.s and that this can occur with physiologically released ACh during repetitive presynaptic nerve activity.