REGULATORY ROLE OF ENTERIC KAPPA-OPIOID RECEPTORS IN HUMAN COLONIC MOTILITY

The effects of different kappa opioid agonists and antagonists on spontaneous mechanical activities and responses to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human sigmoid colon were studied. A superfusion apparatus was used to record isometric contractions. Exogenously added kappa agonists did not modify spontaneous contractile activities on either type of strip. Nerve stimulation induced a triphasic response composed of a first contraction (C1) followed by a relaxation (C2) and an off-contraction (C3); this response was mediated by cholinergic excitatory nerves and non-adrenergic, non-cholinergic excitatory and inhibitory nerves. Dynorphin 1-13 and the synthetic kappa agonist trans-3,4-dichloro-N-methyl-N-(2-[1pyrolidinyl ]-cyclohexyl) dramatically decreased the amplitude of the excitatory components C1 and C3. The effects of both kappa agonists were blocked in presence of the kappa antagonist Nor-Binaltorphimine. The delta antagonist ICI 174864 did not prevent the inhibition of the contractions C1 and C3 induced by dynorphin. Therefore, these data suggest that kappa receptors are involved in the neuroregulation of smooth muscle of human colon and mediate inhibition of cholinergic and non-cholinergic excitatory transmission within myenteric plexus.