Pharmacological study of dihydroetorphine in cloned mu-, delta- and kappa-opioid receptors

Eur J Pharmacol. 1995 Nov 30;291(3):367-73. doi: 10.1016/0922-4106(95)90078-0.

Abstract

We investigated the binding characteristics of dihydroetorphine, 7,8-dihydro-7 alpha-[1-(R)-hydroxy-1-methylbutyl]-6, 14-endoethanotetrahydro-oripavine, and its effect on the inhibitory system of cyclic AMP production using cloned mu-, delta- and kappa-opioid receptors expressed on Chinese hamster ovary cells. The Ki values of dihydroetorphine for the mu-, delta- and kappa-opioid receptors were 4.5 x 10(-10). 1.8 x 10(-9) and 5.7 x 10(-10) M, respectively. On the other hand, those of morphine were 1.9 x 10(-9), 1.4 x 10(-6) and 1.3 x 10(-7) M, respectively. Through all of these three types of opioid receptors, dihydroetorphine inhibited forskolin (10 microM)-stimulated cyclic AMP production via pertussis toxin-sensitive G protein(s), and the inhibitory effects were antagonized by co-application with opioid receptor antagonists. The IC50 values of dihydroetorphine for the inhibition of cyclic AMP production through the mu-, delta- and kappa-opioid receptors were 4.2 x 10(-11), 8.6 x 10(-10) and 4.3 x 10(-9) M. respectively. On the other hand, those of morphine were 2.6 x 10(-8), 2.6 x 10(-6) and 1.9 x 10(-6) M, respectively. These results indicate that dihydroetorphine, unlike morphine which preferentially binds the mu-opioid receptor, binds not only mu- but also delta- and kappa-opioid receptors with high affinity and acts as a more potent agonist than morphine for all of the three types of receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cloning, Molecular
  • Colforsin / pharmacology
  • Cricetinae
  • Etorphine / analogs & derivatives*
  • Etorphine / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology
  • Pertussis Toxin
  • Receptors, Opioid, delta / drug effects*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / drug effects*
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / drug effects*
  • Receptors, Opioid, mu / metabolism
  • Recombinant Proteins / metabolism
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Narcotic Antagonists
  • Narcotics
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Recombinant Proteins
  • Virulence Factors, Bordetella
  • Colforsin
  • Etorphine
  • Pertussis Toxin
  • 18,19-dihydroetorphine