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Published on: July 3, 2015
Mutation S363A in the human delta-opioid receptor selectively reduces down-regulation by a peptide agonist
Edita Navratilova1, Eva V Varga, Dagmar Stropova
1Department of Pharmacology, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Abstract:
Chemically distinct opioid agonists have different abilities to down-regulate opioid receptors. The present study investigated the role of Ser(363) in human delta-opioid receptor down-regulation by a delta-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-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]N,N-diethylbenzamide (SNC80). These results demonstrate that the molecular mechanism of the human delta-opioid receptor down-regulation is agonist-specific.
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