Mutation S363A in the human δ-opioid receptor selectively reduces down-regulation by a peptide agonist

Abstract

Chemically distinct opioid agonists have different abilities to down-regulate opioid receptors. The present study investigated the role of Ser 363 in human δ-opioid receptor down-regulation by a δ-selective peptide- and non-peptide agonist. Cyclic[ d-Pen 2, d-Pen 5]enkephalin (DPDPE)-mediated down-regulation was significantly attenuated by a S363A mutation. In contrast, this mutation had no effect on down-regulation by (+)-4-[(α R)-α-((2 S,5 R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl] N, N-diethylbenzamide (SNC80). These results demonstrate that the molecular mechanism of the human δ-opioid receptor down-regulation is agonist-specific.