Differential binding properties of oripavines at cloned mu- and delta-opioid receptors

Eur J Pharmacol. 1999 Aug 13;378(3):323-30. doi: 10.1016/s0014-2999(99)00460-4.

Abstract

This study examines the possibility that oripavine opioid receptor agonists bind equally to both high and low affinity states of the mu-opioid receptor. Studies were performed in C6 cells expressing mu- or delta-opioid receptors; high and low agonist affinity states of the receptors were defined by the absence and presence, respectively of Na+ ions and the GTP analog Gpp(NH)p. At the mu-opioid receptor dihydroetorphine and etorphine were full agonists, buprenorphine had moderate efficacy while diprenorphine was an antagonist. At the delta-opioid receptor, dihydroetorphine, etorphine, and diprenorphine had moderate efficacy while buprenorphine was an antagonist. The binding affinities of the oripavines at the mu-opioid receptor decreased only one to 2-fold in the presence of NaCl and Gpp(NH)p. In contrast, decreases in oripavine affinity at the delta-opioid receptor correlated with delta-opioid receptor efficacy. The ability of oripavine agonists to bind with high affinity to the low agonist affinity state of the nu-opioid receptor may explain the high potencies of these compounds in vivo.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Benzamides / pharmacology
  • Binding, Competitive / drug effects
  • Buprenorphine / pharmacology
  • Cloning, Molecular
  • Diprenorphine / metabolism
  • Dose-Response Relationship, Drug
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Etorphine / analogs & derivatives
  • Etorphine / pharmacology
  • Fentanyl / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Morphine / pharmacology
  • Naloxone / metabolism
  • Piperazines / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Opioid, delta / agonists
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / metabolism*
  • Sulfur Radioisotopes
  • Thebaine / analogs & derivatives*
  • Thebaine / metabolism
  • Thebaine / pharmacology
  • Tritium
  • Tumor Cells, Cultured

Substances

  • Analgesics, Opioid
  • Benzamides
  • Piperazines
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Sulfur Radioisotopes
  • Tritium
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Diprenorphine
  • Thebaine
  • Naloxone
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Buprenorphine
  • Etorphine
  • oripavine
  • Morphine
  • 18,19-dihydroetorphine
  • Fentanyl