TONIC MODULATION OF NEUROTRANSMITTER RELEASE IN THE GUINEA-PIG MYENTERIC PLEXUS - EFFECT OF MU-OPIOID AND KAPPA-OPIOID RECEPTOR BLOCKADE AND OF CHRONIC SYMPATHETIC DENERVATION

We have studied the effects of mu- and kappa-opioid receptor blockade on endogenous acetylcholine and noradrenaline overflow from the myente ric plexus of the guinea-pig isolated colon. Cyprodime (putative mu-se lective antagonist) and nor-binaltorphimine (kappa-selective antagonis t) had a concentration-dependent facilitatory effect on both acetylcho line and noradrenaline overflow. Moreover, in colonic specimens obtain ed from sympathetically denervated animals, the effect of opioid antag onists on acetylcholine overflow was significantly higher with respect to normal preparations. Evidence is thus given in favour of an involv ement of mu- and kappa-opioid receptor pathways in the tonic modulatio n of neurotransmitter release at the colonic level. Enhanced sensitivi ty to the effect of mu and kappa antagonists after chronic sympathetic denervation is strongly suggestive for the existence of a functional link between opioid and adrenergic pathways in this model.