Agonist-specific regulation of the δ-opioid receptor

Eva V. Varga, Edita Navratilova, Dagmar Stropova, Janelle Jambrosic, William R Roeske, Henry I. Yamamura

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Delta opioid receptor (DOR) agonists are attractive potential analgesics, since these compounds exhibit strong antinociceptive activity with relatively few side effects. In the past decade, several novel classes of δ-opioid agonists have been synthesized. Recent experimental data indicate that structurally distinct opioid agonists interact differently with the δ-opioid receptor. Consequently, individual agonist-bound DOR conformations may interact differently with intracellular proteins. In the present paper, after a brief review of the cellular processes that contribute to homologous desensitization of the DOR signaling, we shall focus on experimental data demonstrating that chemically different agonists differ in their ability to phosphorylate, internalize, and/or down-regulate the DOR. Homologous regulation of the opioid receptor signaling is thought to play an important role in the development of opioid tolerance. Therefore, agonist-specific differences in DOR regulation suggest that by further chemical modification, δ-selective opioid analgesics can be designed that exhibit a reduced propensity for analgesic tolerance.

Original languageEnglish (US)
Pages (from-to)599-612
Number of pages14
JournalLife Sciences
Volume76
Issue number6
DOIs
StatePublished - Dec 24 2004

Fingerprint

delta Opioid Receptor
Opioid Receptors
Opioid Analgesics
Analgesics
Chemical modification
Conformations
Down-Regulation
Proteins

Keywords

  • Agonist-directed trafficking
  • Delta opioid receptor
  • Down-regulation
  • Homologous regulation
  • Internalization
  • Receptor desensitization

ASJC Scopus subject areas

  • Pharmacology

Cite this

Varga, E. V., Navratilova, E., Stropova, D., Jambrosic, J., Roeske, W. R., & Yamamura, H. I. (2004). Agonist-specific regulation of the δ-opioid receptor. Life Sciences, 76(6), 599-612. https://doi.org/10.1016/j.lfs.2004.07.020

Agonist-specific regulation of the δ-opioid receptor. / Varga, Eva V.; Navratilova, Edita; Stropova, Dagmar; Jambrosic, Janelle; Roeske, William R; Yamamura, Henry I.

In: Life Sciences, Vol. 76, No. 6, 24.12.2004, p. 599-612.

Research output: Contribution to journalArticle

Varga, EV, Navratilova, E, Stropova, D, Jambrosic, J, Roeske, WR & Yamamura, HI 2004, 'Agonist-specific regulation of the δ-opioid receptor', Life Sciences, vol. 76, no. 6, pp. 599-612. https://doi.org/10.1016/j.lfs.2004.07.020
Varga EV, Navratilova E, Stropova D, Jambrosic J, Roeske WR, Yamamura HI. Agonist-specific regulation of the δ-opioid receptor. Life Sciences. 2004 Dec 24;76(6):599-612. https://doi.org/10.1016/j.lfs.2004.07.020
Varga, Eva V. ; Navratilova, Edita ; Stropova, Dagmar ; Jambrosic, Janelle ; Roeske, William R ; Yamamura, Henry I. / Agonist-specific regulation of the δ-opioid receptor. In: Life Sciences. 2004 ; Vol. 76, No. 6. pp. 599-612.
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