Opioid delta-receptor involvement in supraspinal and spinal antinociception in mice.
The possibility that the opioid delta-receptor mediates antinociception in tests where heat is the noxious stimulus was investigated using highly selective mu- and delta-agonist and -antagonists. Antinociceptive dose-response curves were constructed for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO; morphine) and delta ([D-Pen2,D-Pen5]enkephalin, DPDPE)-agonists in the absence, and in the presence of the mu non-surmountable antagonist, beta-funaltrexamine (beta-FNA) or the delta-antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is alpha-amino-isobutyric acid). Agonists and ICI 174,864 were given alone in the same intracerebroventricular (i.c.v.) or intrathecal (i.th.) injection to mice 20 min prior to testing in the warm-water (55 degrees C) tail-withdrawal test (+10 min for i.th. DPDPE); beta-FNA was given as a single i.c.v. or i.th. pretreatment dose (20 and 0.01 nM, respectively) 4 h prior to testing. I.c.v. pretreatment with beta-FNA resulted in a rightward displacement of the DAGO and morphine antinociceptive dose-response lines, but failed to displace the i.c.v. DPDPE curve. Similarly, i.th. pretreatment with beta-FNA displaced the i.th. morphine dose-response curve to the right without affecting the i.th. DPDPE antinociceptive dose-response line. ICI 174,864 (1 and 3 micrograms) produced a dose-related antagonism of i.c.v. or i.th. DPDPE, but did not alter the antinociceptive effects of DAGO or morphine given by the same routes. Co-administration of ICI 174,864 (3 micrograms) with i.c.v. morphine in beta-FNA pretreated (but not control) mice resulted in a further rightward displacement of the morphine dose-response line.(ABSTRACT TRUNCATED AT 250 WORDS)
Heyman
J S
JS
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Mulvaney
S A
SA
Mosberg
H I
HI
Porreca
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D006358:Hot Temperature; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*
D004338:Drug Combinations; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine