Mutation S363A in the human delta-opioid receptor selectively reduces down-regulation by a peptide agonist.
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.
Navratilova
Edita
E
Department of Pharmacology, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Varga
Eva V
EV
Stropova
Dagmar
D
Jambrosic
Janelle C
JC
Roeske
William R
WR
Yamamura
Henry I
HI
D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D001549:Benzamides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000819:agonists* / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000235:genetics*; D012694:Serine / Q000235:genetics
D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D012694:Serine; D020881:Enkephalin, D-Penicillamine (2,5)-; D000409:Alanine