title: [3H][D-Ala2,NMePhe4,Gly-ol5]-enkephalin (mu-opioid) binding in beige-J mice.
abstract: Tritiated [D-Ala2,NMePhe4,Gly-ol5]-enkephalin ([3H]DAGO) was used to examine mu-opioid receptor number and mu-ligand binding in brain synaptic membranes (P2 fraction) from C57BL/6J-bgJ/bgJ (beige-J) mice, a strain with combined deficiencies in immunological function (resembling Chediak-Higashi syndrome) and analgesic response to mu-opioid agonists such as morphine and DAGO. As controls, white mice, beige-J littermates (normally responsive to mu-opioid agonists), and a known mu-deficient strain (CXBK) were also examined. Neither the KD (0.47 to 0.49 nM) nor the Bmax (153 to 168 fmol/mg protein) determined for beige-J mice was significantly different from values determined for littermates or white mice. In contrast, the Bmax of CXBK mice (66 fmol/mg protein) was clearly less than that of the other strains. The analgesic defect of beige-J mice, therefore, is not likely due to an insufficient number of mu-opioid receptors, as it presumably is in CXBK mice. Carbachol (200 micrograms/ml), which partly corrects the analgesic defect of beige-J mice, had no effect on [3H]DAGO binding either acutely in vitro or chronically ex vivo after administration to beige-J mice for three weeks. Hence, the analgesic defect of beige-J mice appears to be due to some defect in the mu-opioid receptor-effector coupling mechanism or to some endogenous substance that inhibits binding of mu-opioid ligands to otherwise functional receptors.
authors.affiliation: Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477.
authors.forename: R B
authors.initials: RB
authors.lastname: Raffa
authors.forename: W J
authors.initials: WJ
authors.lastname: Baldy
authors.forename: R P
authors.initials: RP
authors.lastname: Shank
authors.forename: J R
authors.initials: JR
authors.lastname: Mathiasen
authors.forename: J L
authors.initials: JL
authors.lastname: Vaught
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D012016:Reference Values; D013045:Species Specificity; D013570:Synaptic Membranes / Q000378:metabolism*; D014316:Tritium
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002217:Carbachol