Opioids increase potassium conductance in submucous neurones of guinea‐pig caecum by activating δ‐receptors

Abstract

Intracellular records were made from neurones in the submucous plexus of the guinea-pig caecum. [Met5]enkephalin, [Leu5]enkephalin, [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ser2,Leu5]enkephalin-Thr (DSLET) hyperpolarized the membrane when applied in concentrations of 30 nm-10 microM. Normorphine, [D-Ala2, MePhe4,Gly5]enkephalin-ol (DAGO), [D-Ala2,MePhe4,Met(0)5]enkephalin-ol (FK33824), dynorphin A and tifluadom had no effect at concentrations up to 10 microM. The hyperpolarization resulted from an increase in the membrane potassium conductance. Hyperpolarizations induced by [Met5]enkephalin were antagonized competitively by naloxone and by N-bisallyl[aminoisobutyrate2,3, Leu5]enkephalin (ICI 174864). The Schild plots for these antagonisms had slopes not different from one, and the dissociation equilibrium constants among individual neurones were 5-50 nM for naloxone and 5-60 nM for ICI 174864. The results indicate that the opioid receptors on guinea-pig submucous neurones which are coupled to potassium channels are of the delta-type.