Abstract
Down-regulation of the δ-opioid receptor contributes to the development of tolerance to δ-opioid receptor agonists. The involvement of the carboxy terminus of the mouse δ-opioid receptor in peptide agonist-mediated down-regulation has been established. In the present study, we examined the down-regulation of the truncated human δ-opioid receptor by structurally distinct δ-opioid receptor agonists. Chinese hamster ovary (CHO) cells, expressing the full-length or truncated epitope-tagged human δ-opioid receptors were incubated with various δ-opioid receptor agonists (100 nM, 24 h), and membrane receptor levels were determined by [3H]naltrindole saturation binding. Each δ-opioid receptor agonist tested down-regulated the full-length receptor. Truncation of the carboxy terminus abolished down-regulation by all δ-opioid receptor agonists, except SNC80 ((+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- methoxybenzyl]N,N-diethylbenzamide). In addition, truncation of the C-terminus completely attenuated [D-Pen2-D-Pen5]enkephalin (DPDPE), but not SNC80-mediated [32P] incorporation into the protein immunoreactive with an anti-epitope-tagged antibody. These findings suggest that SNC80-mediated phosphorylation and down-regulation of the human δ-opioid receptor involves other receptor domains in addition to the carboxy terminus. Pertussis toxin treatment did not block SNC80-mediated down-regulation of the truncated Et-hDOR, indicating that the down-regulation is independent of Gi/o protein activation and subsequent downstream signaling.
Original language | English (US) |
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Pages (from-to) | 9-16 |
Number of pages | 8 |
Journal | European Journal of Pharmacology |
Volume | 459 |
Issue number | 1 |
DOIs | |
State | Published - Jan 10 2003 |
Keywords
- Agonist-directed trafficking
- Down-regulation
- Human
- Pertussis toxin
- Phosphorylation
- δ-Opioid receptor
ASJC Scopus subject areas
- Pharmacology