Region-dependent G-protein activation by kappa-opioid receptor agonists in the mouse brain

Neurosci Lett. 2004 Feb 12;356(2):145-7. doi: 10.1016/j.neulet.2003.09.034.


The G-protein activations induced by kappa-opioid receptor agonists, (-)U50,488H, U69,593 and TRK-820 in the mouse lower midbrain, striatum and limbic forebrain were determined by monitoring guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding. All kappa-opioid receptor agonists produced approximately 40, 20 and 10% increases of [35S]GTP gamma S binding over baseline in the lower midbrain, striatum and limbic forebrain, respectively. The increases of [35S]GTP gamma S binding induced by kappa-opioid receptor agonists were completely reversed by the selective kappa-opioid receptor antagonist, norbinaltorphimine (norBNI), in all brain regions. The intrinsic activities of kappa-opioid receptor agonists for G-protein activation in brain regions observed in the present study are not correlated with densities of kappa-opioid receptor binding sites from previous reports. The present results suggest that the catalytic efficiency of kappa-opioid receptor-G-protein coupling may be variable in different brain regions.

Publication types

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

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Animals
  • Benzeneacetamides / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • GTP-Binding Proteins / drug effects*
  • GTP-Binding Proteins / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacokinetics
  • Male
  • Mice
  • Morphinans / pharmacology
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Narcotic Antagonists
  • Pyrrolidines / pharmacology
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Spiro Compounds / pharmacology


  • Benzeneacetamides
  • Morphinans
  • Narcotic Antagonists
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Spiro Compounds
  • TRK 820
  • norbinaltorphimine
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • GTP-Binding Proteins
  • U 69593