Opioid mu receptor subtypes (possibly mu 1 and mu 2) revealed by morphine-induced antinociception vs endothelin-1 in recombinant inbred CXBK mice.
Morphine was administered intracerebroventricularly to normal or recombinant inbred CXBK (mu-opioid receptor deficient) mice and antinociception was determined against two different stimuli. Morphine-induced antinociception against acetylcholine was strain-dependent, whereas against endothelin-1 it was not. The antinociception was mediated via opioid mu receptors (blocked by beta-FNA, but not naltrindole, ICI 174,864 or nor-BNI) through separate pathways, one naloxonazine-sensitive and the other naloxonazine-insensitive. Taken together, these results appear to demonstrate supraspinal morphine-induced antinociception through distinct subtypes of the mu opioid receptor, supporting the possibility of novel subtype-selective therapeutic agents with greater separation between analgesia and side-effects or physical dependence. Furthermore, the methodology described herein provides model systems for the in vivo screening of such agents.
Raffa
R B
RB
Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Schupsky
J J
JJ
D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology*
D016232:Endothelins; D017450:Receptors, Opioid, mu; D009020:Morphine