Relationship of mu opioid receptor binding to activation of G-proteins in specific rat brain regions

Biochem Pharmacol. 2000 Jun 1;59(11):1395-401. doi: 10.1016/s0006-2952(00)00272-0.


This study investigated the relationship between mu receptor binding and mu agonist activation of G-proteins in the rat brain. To directly compare agonist potencies in receptor binding (K(i) values) and G-protein activation (K(s) values), both agonist-stimulated [(35)S]guanosine-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) and [(3)H]naloxone binding assays were conducted under identical conditions, using the full mu agonist [d-Ala(2), N-Me(4), Gly(5)-ol]-enkephalin (DAMGO). DAMGO exhibited biphasic competition of [(3)H]naloxone binding and stimulation of [(35)S]GTPgammaS binding in most regions. Whereas the high-affinity component represented a large percentage (50-80%) of total receptor sites, the high-affinity component of DAMGO-stimulated [(35)S]GTPgammaS binding was much lower, <30% of the total, and in most regions significant stimulation of [(35)S]GTPgammaS binding did not occur until the high-affinity binding sites were completely occupied. Moreover, the low-affinity potencies for DAMGO in receptor binding and G-protein activation were the same across different regions. Receptor-transducer amplification factors were calculated by the ratio of the apparent B(max) of net agonist-stimulated [(35)S]GTPgammaS binding to the B(max) of receptor binding. Amplification factors for the nine regions examined were relatively high and varied significantly across regions, from a ratio of 8 in the thalamus to 38 in the cortex, suggesting that the efficiency of mu opioid receptor coupling to G-proteins varies across brain regions.

Publication types

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

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Brain / metabolism*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • In Vitro Techniques
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / metabolism*
  • Sulfur Radioisotopes
  • Tritium


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, Opioid, mu
  • Sulfur Radioisotopes
  • Tritium
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naloxone
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • GTP-Binding Proteins