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 som e aspects of opioid dependence, tolerance, and supersensitivity. To st udy the mechanism of this receptor modulation we have employed CHO cel ls containing a single, transfected opioid receptor of the delta-type. When forskolin was employed to elevate cAMP the reduction affected by 10 mu M DADLE was counteracted by preincubation of the cells with GM1 . No effect was observed with GD1a, GD1b, GT1b GM3, or the GM1 derivat ive, GM1-OH. In pertussis toxin-treated cells 10 nM DADLE increased ba sal levels of cAMP after preincubation with as little as 10 nM GM1. Th e results suggest conformational alteration of the opioid receptor fro m a form coupled primarily to G(i)/G(o) to one also capable of interac ting with G(s).