Modulation of peristalsis in the guinea-pig isolated small intestine by exogenous and endogenous opioids

Abstract

1. A recording method was developed to measure physiological parameters of the preparatory and emptying phases of peristalsis in vitro. This method enabled measurement of: the compliance of the intestinal wall during the preparatory phase (a reflection of the resistance of the wall to distension); longitudinal muscle contraction during the preparatory phase; the threshold volume required to trigger the emptying phase; the maximal ejection pressure and the average power generated during the emptying phase, which reflects the rate at which the intestine performs work. Modulation of these parameters by exogenous and endogenous opioids acting at mu, kappa and delta opioid receptors was investigated. 2. The compliance of the intestinal wall during the preparatory phase was reduced by the mu opioid receptor agonist, [D-Ala2, N-methyl-Phe4, Gly5-ol] enkephalin (DAMGO) but not by the kappa agonist, dynorphin, or the delta agonist, [D-penicillamine2, D-penicillamine5] enkephalin (DPDPE). Reflex contraction of the longitudinal muscle during the preparatory phase was inhibited by DAMGO, dynorphin and DPDPE. The threshold volume required to trigger the emptying phase of peristalsis was increased by DAMGO, dynorphin and DPDPE. 3. The maximal ejection pressure generated during the emptying phase was reduced by dynorphin and DPDPE, but not by DAMGO. The average power generated by the intestine when emptying was not altered by any of the agonists. 4. Electrically stimulated contractions of longitudinal muscle in strips of longitudinal muscle-myenteric plexus were not inhibited by DPDPE. Similarly, DPDPE did not significantly inhibit electrically induced contraction of circular muscle in strips of circular muscle-myenteric plexus.5. Each of the agonist effects on peristaltic parameters was antagonized by the appropriate antagonist:D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) (mu), norbinaltorphimine (nor-BNI) (kappa), naltrindole(delta).6. It is concluded that mu and kappa agonists act primarily on excitatory circular and longitudinal muscle motor neurones. The delta agonist probably acts on enteric neurones presynaptic to excitatory circular and longitudinal muscle motor neurones.7. Antagonists for mu, delta and kappa receptors did not affect any parameters of peristalsis when the intestine emptied against a low resistance. However, when emptying against a high outflow resistance, the average power generated by the intestine was increased by the kappa antagonist, nor-BNI, but not by CTOP or naltrindole.8. It is concluded that endogenous opioids appear to have little role in peristalsis when the intestine is working against a low outflow resistance. However endogenous opioids, acting primarily at kappa receptors,provide a braking mechanism by inhibiting the emptying phase of peristalsis in conditions in which the intestine empties against a higher resistance.