An analysis of possible nervous mechanisms involved in the peristaltic reflex.

1. The effects of drugs on peristalsis and on the contractions of the two muscle coats of the isolated guinea-pig ileum in response to co-axial electrical stimulation have been studied.2. Co-axial stimulation (0.1 msec pulses) never produces simultaneous contraction of both muscle coats. When one muscle contracts, the other either relaxes or remains quiescent.3. The circular muscle contraction has two components. The first is reflex in origin and is brought about either by distension of the gut with increasing intraluminal filling or by the contraction of the longitudinal muscle in response to electrical stimulation at low frequency (1/sec), provided this raises the intraluminal pressure to the threshold for eliciting the circular muscle contraction. As the circular muscle contracts, the longitudinal muscle relaxes although stimulation continues. If the circular muscle contraction is prevented by reducing the intraluminal filling, or by adding a ganglion-blocking drug, the longitudinal muscle remains contracted until withdrawal of the stimulus.4. In the presence of hyoscine, the reflex contraction of the circular muscle is unimpaired but, since the longitudinal muscle contraction is abolished, a higher intraluminal pressure is required to elicit the reflex.5. The second component of the circular muscle contraction appears in response to electrical stimulation at high frequency (3-10/sec), upon withdrawal of electrical stimulation. This delay indicates the simultaneous stimulation of a dominant inhibitory innervation.6. The excitatory nerves to the circular muscle require a higher frequency of stimulation than those to the longitudinal muscle, which respond to single shocks.7. Cholinergic blocking agents (hyoscine, morphine, hemicholinium and botulinum toxin) antagonize the responses of the longitudinal muscle to co-axial stimulation without affecting those of the circular muscle, thus suggesting that the excitatory fibres to the circular muscle are not cholinergic. Prostaglandins (E(1) and E(2)) selectively antagonize the circular muscle contractions evoked by co-axial stimulation. Tetrodotoxin blocks both longitudinal and circular muscle responses.8. Dimethylphenylpiperazinium (DMPP) and 5-hydroxytryptamine (5-HT) stimulate ganglia but have no direct action on the smooth muscle of guinea-pig ileum.9. During a maintained contraction of the longitudinal muscle in the presence of high concentrations of acetylcholine (2.5 x 10(-7) to 10(-6) g/ml.) a contraction of the circular muscle accompanied by a relaxation of the longitudinal muscle is elicited by distension of the gut, and by co-axial stimulation. Similar reciprocal responses are produced by 5-HT or by DMPP and they are finally blocked by DMPP.10. These results are consistent with the hypothesis that in the myenteric plexus there exists an arrangement of nerves which ensures that the two muscle coats of the intestine do not contract simultaneously but are activated reciprocally so that when one muscle layer contracts the other relaxes or is prevented from contracting.