Na+ ions and Gpp(NH)p selectively inhibit agonist interactions at mu- and kappa-opioid receptor sites in rabbit and guinea-pig cerebellum membranes

Eur J Pharmacol. 1985 Nov 5;117(2):223-32. doi: 10.1016/0014-2999(85)90607-7.


Rabbit and guinea-pig cerebellum membrane preparations contain a high proportion (greater than 80%) of mu- and of kappa-opioid binding sites, respectively. These preparations were therefore used to compare the regulation of binding of mu- and of kappa-opioid agonists and antagonists by sodium ions and by guanyl-5'-yl imidodiphosphate. We report here that Na+ ions, Gpp(NH)p and most efficiently, the two agents in association selectively inhibited binding of opioid agonists not only in the mu preparation (rabbit cerebellum) but also in the kappa preparation (guinea-pig cerebellum). These allosteric effectors did not inhibit equilibrium binding of antagonists (naloxone, Mr 2266 or diprenorphine) in the two preparations. Taken together these results suggest that occupancy either of the mu-receptor by a mu-agonist or of the kappa-receptor by a kappa-agonist may be accompanied by similar if not identical molecular events. They also suggest a method to rapidly screen newly designed drugs as mu- or kappa-opioid agonists or antagonists.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics, Opioid / metabolism
  • Animals
  • Benzomorphans / metabolism
  • Binding, Competitive
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Diprenorphine / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / metabolism
  • Etorphine / metabolism
  • Guanosine Triphosphate / analogs & derivatives*
  • Guanylyl Imidodiphosphate / pharmacology*
  • Guinea Pigs
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Naloxone / metabolism
  • Pyrrolidines / metabolism
  • Rabbits
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Sodium / pharmacology*


  • Analgesics, Opioid
  • Benzomorphans
  • Enkephalins
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Diprenorphine
  • Guanylyl Imidodiphosphate
  • Naloxone
  • Etorphine
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Guanosine Triphosphate
  • Sodium
  • bremazocine