Modulation of neurotransmitter release by opioid mu- and kappa-receptors from adrenergic terminals in the myenteric plexus of the guinea-pig colon: effect of alpha2-autoreceptor blockade.

We have studied the effect of [D-Ala(2)-N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO) opioid mu-receptor agonist) and ICI-204,448 (kappa-receptor agonist) on endogenous noradrenaline release in the guinea-pig isolated distal colon. DAMGO enhances noradrenaline overflow and this effect is antagonized by naloxone (PIC50=10.27) and nor-binaltorphimine (pIC(50)=7.97), and concentration-dependently turned into inhibition by yohimbine. ICI-204,448 inhibits noradrenaline overflow and is antagonized by naloxone(pIC(50)=9.38) and nor-binaltorphimine (pIC(50)=10.48), but is not affected by yohimbine. Evidence is thus' given that mu and kappa-opioid receptors modulate noradrenaline release in the guinea-pig colon. Modifications by yohimbine of the effect of DAMGO indicate the existence of a functional relationship between mu-receptors and alpha(2)-autoreceptors in this model.