title: Acute antinociceptive tolerance and partial cross-tolerance to endomorphin-1 and endomorphin-2 given intrathecally in the mouse.
abstract: The effect of pretreatment with endomorphin-1 (EM-1) or endomorphin-2 (EM-2) given intrathecally (i.t.) on the tail-flick inhibition induced by subsequent i.t. injection of EM-1 or EM-2 was studied in CD-1 mice. Pretreatment with EM-1 (32.7 nM) for 1-3 h, but not 4 h, attenuated the tail-flick inhibition induced by i.t. EM-1 (16.3 nM), while pretreatment with EM-2 (70 nM) for 0.5-1.5 h, but not 2 h, attenuated tail-flick inhibition induced by i.t. EM-2 (35 nM). EM-1 (32.7 nM) pretreatment for 1.5 h produced 5.3- and only 2.4-folds shift to the right of the dose-response curves for EM-1- and EM-2-induced tail-flick inhibition, respectively, while EM-2 (70 nM) pretreatment for 1 h caused 4.3- and 4.5-folds shift to the right for EM-2- and EM-1-induced tail-flick inhibition, respectively. Thus, mice made antinociceptive tolerant to EM-1 were partially cross-tolerant to EM-2 and mice made antinociceptive tolerant to EM-2 were completely cross-tolerant to EM-1. It is proposed that EM-1- and EM-2-induced antinociception are mediated by the stimulation of two different subtypes of mu-opioid receptors in mouse spinal cord; one subtype is stimulated by both EM-1 and EM-2, and another subtype is stimulated by EM-2.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Hsiang-En
authors.initials: HE
authors.lastname: Wu
authors.forename: Moses
authors.initials: M
authors.lastname: Darpolor
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2