Interaction of the delta-opioid receptor with GM1 ganglioside: conversion from inhibitory to excitatory mode.

Previous studies have shown GM1 ganglioside to play a crucial role in regulating excitatory opioid receptor function, which may underlie some aspects of opioid dependence, tolerance, and supersensitivity. To study the mechanism of this receptor modulation we have employed CHO cells containing a single, transfected opioid receptor of the delta-type. When forskolin was employed to elevate cAMP the reduction affected by 10 microM DADLE was counteracted by preincubation of the cells with GM1. No effect was observed with GD1a, GD1b, GT1b GM3, or the GM1 derivative, GM1-OH. In pertussis toxin-treated cells 10 nM DADLE increased basal levels of cAMP after preincubation with as little as 10 nM GM1. The results suggest conformational alteration of the opioid receptor from a form coupled primarily to G(i)/G(o) to one also capable of interacting with G(s).