Differential down-regulation of the human δ-opioid receptor by SNC80 and [ d-Pen 2, d-Pen 5]enkephalin

We examined the contribution of the human δ-opioid receptor carboxyl terminal tail to (+)-4-[(α R)-α-((2 S,5 R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N, N-diethylbenzamide (SNC80)- and cyclic[ d-Pen 2, d-Pen 5]enkephalin (DPDPE)-mediated receptor down-regulation. Both SNC80 and DPDPE mediated down-regulation of an epitope tagged human δ-opioid receptor. Truncation of the human δ-opioid receptor after Gly 338 blocked DPDPE-mediated down-regulation. However, SNC80 mediated significant down-regulation of the truncated receptor. These findings suggest that SNC80-mediated down-regulation involves receptor domains in addition to the carboxyl terminal tail.