title: Acute antinociceptive tolerance and asymmetric cross-tolerance between endomorphin-1 and endomorphin-2 given intracerebroventricularly in the mouse.
abstract: Development of tolerance in mice pretreated intracerebroventricularly with mu-opioid receptor agonist endomorphin-1, endomorphin-2, or [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO) was compared between endomorphin-1- and endomorphin-2-induced antinociception with the tail-flick test. A 2-h pretreatment with endomorphin-1 (30 nmol) produced a 3-fold shift to the right in the dose-response curve for endomorphin-1. Similarly, a 1-h pretreatment with endomorphin-2 (70 nmol) caused a 3.9-fold shift to the right for endomorphin-2. In cross-tolerance experiments, pretreatment with endomorphin-2 (70 nmol) caused a 2.3-fold shift of the dose-response curve for endomorphin-1, whereas pretreatment with endomorphin-1 (30 nmol) caused no change of the endomorphin-2 dose-response curve. Thus, mice acutely tolerant to endomorphin-1 were not cross-tolerant to endomorphin-2, although mice made tolerant to endomorphin-2 were partially cross-tolerant to endomorphin-1; an asymmetric cross-tolerance occurred. Pretreatment with DAMGO 3 h before intracerebroventricular injection of endomorphin-1, endomorphin-2, or DAMGO attenuated markedly the antinociception induced by endomorphin-1 and DAMGO but not endomorphin-2. It is proposed that two separate subtypes of mu-opioid receptors are involved in antinociceptive effects induced by endomorphin-1 and endomorphin-2. One subtype of opioid mu-receptors is stimulated by DAMGO, endomorphin-1, and endomorphin-2, and another subtype of mu-opioid receptors is stimulated solely by endomorphin-2.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Wu
authors.forename: K C
authors.initials: KC
authors.lastname: Hung
authors.forename: H
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: J M
authors.initials: JM
authors.lastname: Fujimoto
authors.forename: L F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C105294:endomorphin 2