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

Journal Article · · Life Sci.; (United States)

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 (/sup 3/H)morphine and (/sup 3/H)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 (/sup 3/H)leucine enkephalin binding were considerably enhanced by the conjugations at the 6-position, whereas the potencies against (/sup 3/H)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 /sup +/-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 the authors laboratory. 24 references, 2 figures, 1 table.

Research Organization:
Kyushu Univ., Fukuoka, Japan
OSTI ID:
6075922
Journal Information:
Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 41:12; ISSN LIFSA
Country of Publication:
United States
Language:
English