Non-synaptic cholinergic modulation of neurogenic twitches of the guinea-pig ileum

The effect of cholinergic and anticholinergic compounds on conduction of neuronal excitation has been studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment (10 mm) so that the aboral segment might be also invaded, eventually. Drugs were added to the middle segment to affect neuronal propagation (non-synaptic effects) which was monitored by twitch height of the aboral segment. The application of acetylcholine to the middle segment augmented aboral twitches. The effects of nicotine, pilocarpine and oxotremorine were selectively blocked by (+)-tubocurarine, pirenzepine and atropine, respectively. The effect of acetylcholine was suppressed by pirenzepine and atropine and mimicked by doubling of KCl concentration. The effect of acetylcholine may be thus explained by the facilitated propagation of nerve action potentials in partially depolarized cholinergic terminals via stimulation of muscarinic receptors. The adenylate cyclase system is not directly involved in the mechanism of muscarinic facilitation of neuronal propagation in the terminals; however, it may participate in the modulation of a final common effector mechanism.