Enhanced binding of morphine and nalorphine to opioid delta receptor by glucuronate and sulfate conjugations at the 6-position

Life Sci. 1987 Sep 21;41(12):1457-64. doi: 10.1016/0024-3205(87)90710-7.


Effect of the modification of morphine and nalorphine by glucuronate and sulfate conjugations at the 3- and 6-positions on the binding to opioid receptors was examined in a particulate fraction of rat brain. Competing potencies of both drugs against [3H]morphine and [3H]leucine enkephalin bindings were extremely decreased by either glucuronate or sulfate conjugation at the 3-position. On the other hand, the potencies of morphine and nalorphine against [3H]leucine enkephalin binding were considerably enhanced by the conjugations at the 6-position, whereas the potencies against [3H]morphine binding were decreased. These altered interactions of the conjugates at the 6-position with the two ligands were attributed to their enhanced binding to delta-receptor and reduced binding to mu-receptor by Hill plot and modified Scatchard analysis. Resulted comparable and simultaneous interactions with mu- and delta- receptors were assumed to be a cause of the enhanced mu-receptor-directed analgesia of morphine and elevated same receptor-directed antagonistic effect of nalorphine, which have been found previously in our laboratory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enkephalin, Leucine / metabolism
  • Glucuronates / metabolism
  • In Vitro Techniques
  • Male
  • Morphine / metabolism*
  • Morphine Derivatives / metabolism*
  • Nalorphine / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Sulfates / metabolism


  • Glucuronates
  • Morphine Derivatives
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Sulfates
  • Enkephalin, Leucine
  • morphine-6-glucuronide
  • Morphine
  • Nalorphine