Desensitization of mu-opioid receptors does not modify the analgesia induced by an enkephalinase inhibitor.
Acetorphan, an enkephalinase inhibitor, or morphine was injected in mice which had received saline or morphine (32 mg/kg s.c. twice a day on 8 consecutive days) chronically. In the hot-plate test, the analgesia (increase in jump latency) induced by morphine (2 mg/kg i.p.) or by the mu selective opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]enkephalin (DAGO) (1.5, 3 or 6 ng/mouse i.c.v.), was significant in the saline group but was strongly decreased in morphine-pretreated mice. In contrast the analgesic effect of acetorphan (5 mg/kg i.v.) or of the delta selective opioid agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.75, 1.5 or 3 micrograms/mouse i.c.v.) was similar in both groups. These results suggest that the enkephalins protected by acetorphan act on the delta receptor site to produce antinociception.
Bousselmame
R
R
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 du C.N.R.S., Faculté de Médecine and Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Michael-Titus
A
A
Costentin
J
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; C049331:racecadotril; D020881:Enkephalin, D-Penicillamine (2,5)-; D015244:Thiorphan; D015260:Neprilysin