title: Chronic administration of morphine and naltrexone up-regulate[3H][D-Ala2,D-leu5]enkephalin binding sites by different mechanisms.
abstract: Previous studies have demonstrated that chronic administration of morphine up-regulated the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin, without producing a detectable alteration in the higher affinity binding site for [3H][D-ala2,D-leu5]enkephalin (Rothman et al., Eur. J. Pharmac. 124: 113-119, 1986). The experiments reported in this paper tested the hypothesis that chronic administration of morphine and naltrexone up-regulated the binding sites for [3H][D-ala2,D-leu5]enkephalin by different mechanisms. Rats were given either morphine or naltrexone chronically. Chronic administration of morphine up-regulated the lower affinity site, while chronic administration of naltrexone up-regulated both the higher and lower affinity binding sites for [3H][D-ala2,D-leu5]enkephalin. Unlike the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin present in membranes prepared from rats treated with placebo pellets, the lower affinity binding sites which were up-regulated by naltrexone and morphine were partially (naltrexone) or completely (morphine) labile to preincubation for 60 min at 25 degrees C in 50 mM Tris-HCl, pH 7.4, containing 0.4 M NaCl. These data suggest that chronic administration of morphine and naltrexone up-regulate binding sites for [3H][D-ala2,D-leu5]enkephalin through different mechanisms, and that the lower affinity binding sites for [3H][D-ala2, D-leu5]enkephalin which are up-regulated by chronic administration of morphine and naltrexone might differ biochemically from the lower affinity binding sites present in membranes treated with placebo.
authors.affiliation: Laboratory of Preclinical Pharmacology, NIMH, St. Elizabeths Hospital, Washington, DC 20002.
authors.forename: J A
authors.initials: JA
authors.lastname: Danks
authors.forename: F C
authors.initials: FC
authors.lastname: Tortella
authors.forename: J B
authors.initials: JB
authors.lastname: Long
authors.forename: V
authors.initials: V
authors.lastname: Bykov
authors.forename: A E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: K C
authors.initials: KC
authors.lastname: Rice
authors.forename: J W
authors.initials: JW
authors.lastname: Holaday
authors.forename: R B
authors.initials: RB
authors.lastname: Rothman
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D011957:Receptors, Opioid; D012965:Sodium Chloride; D009271:Naltrexone; D009020:Morphine