DELTA-OPIOID RECEPTOR AGONISTS INHIBIT NEUROMUSCULAR-TRANSMISSION IN HUMAN COLON

The present study was undertaken to investigate the possible role of d elta-opioid receptors in the neuroregulation of human colonic motility by using a superfusion model. Spontaneous mechanical activity and res ponses to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human sigmoid colon were studied. Exogenously added delta-opioid receptor agonists did not modify spont aneous contractile activities of either type of strip. Nerve stimulati on induced a triphasic response composed of an initial contraction fol lowed by a relaxation and an off-contraction. This response was mediat ed by cholinergic excitatory nerves and non-adrenergic, non-cholinergi c excitatory and inhibitory nerves. [Met(5)]Enkephalin and the synthet ic delta-opioid receptor agonist [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) significantly decreased the amplitude of the initial contraction and of the off-contraction. The effects of both delta-opioid receptor agon ists were reduced in the presence of either the delta-opioid receptor antagonist, ICI 174864, or another delta-opioid receptor antagonist, n altrindole. ICI 174864 prevented neither the effects of a natural kapp a-opioid receptor agonist, dynorphin-(1-13), nor those of the mu-opioi d receptor agonist, PL017. Therefore, these data suggest that delta-op ioid receptors might be involved in the neuroregulation of smooth musc le of human colon and may mediate inhibition of cholinergic and non-ch olinergic excitatory transmission within the myenteric plexus.