The physiological relevance of low agonist affinity binding at opioid mu-receptors

Br J Pharmacol. 1988 Jun;94(2):625-31. doi: 10.1111/j.1476-5381.1988.tb11569.x.


1. Inhibition constant (Ki) were determined for a range of opioid standards using two binding assays; [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]-GLYOL) binding to guinea-pig brain membranes in HEPES buffer and [3H]-naloxone binding to rat whole brain membranes in Krebs/HEPES buffer. 2. These values were compared with affinity measurements determined by antagonism of GLYOL on the rat isolated vas deferens preparation and by the receptor occlusion technique of Furchgott on the guinea-pig ileum longitudinal muscle, myenteric plexus preparation. 3. Agonists demonstrated markedly reduced binding affinity in the [3H]-naloxone binding assay where binding was conducted in the presence of sodium. 4. A strong correlation was obtained between Ki values from the [3H]-naloxone binding assay and affinity values determined in both isolated tissue preparations. Ki values obtained from [3H]-GLYOL binding did not correlate well with affinity data determined by isolated tissue techniques. 5. These findings suggest that functionally relevant receptors exhibit low agonist affinity.

MeSH terms

  • Animals
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / metabolism*
  • Guinea Pigs
  • Ileum / analysis
  • Ileum / drug effects
  • In Vitro Techniques
  • Male
  • Naloxone / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Opioid / analysis
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, mu
  • Tritium
  • Vas Deferens / analysis
  • Vas Deferens / drug effects


  • Enkephalins
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Tritium
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naloxone