Opioid agonists modulate excitatory and inhibitory neurotransmission in human colon

The effects of different opioid agonists on spontaneous mechanical activity and response to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human colon were studied by using a superfusion apparatus to record isometric contractions. Exogenously added opioid agonists did not modify the spontaneous contractile activities of both types of strips. 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 (NANC) excitatory and inhibitory nerves. The delta-agonists methionine enkephalin, [D-Pen2, D-Pen5] enkephalin (DPDPE) and the kappa-agonists dynorphin, trans-3,4 dichloro-N-methyl-N-(2-[1 pyrolidinyl]-cyclohexyl) (U-50488H) decreased the amplitudes of the contractions C1 and C3 of both strips in a dose-dependent manner. The selective mu-agonist D-alaglymepheglyol (DAGO) decreased the contraction C1 of longitudinal and circular muscle at high dose (1 μM) and often reduced the relaxation C2 of both types of strips at low dose (0.05 μM), finally, naloxone, but only at higher concentrations (1 μM) decreased the C1 amplitude significantly in circular muscle. In conclusion, these data suggest that mu, delta and kappa opioid receptors are involved in the neuro-regulation of smooth muscle of human colon and that opioid agonists modulate both excitatory and inhibitory neurotransmission through an action on cholinergic and non-adrenergic, non-cholinergic neurons.