Modulation of mu-mediated antinociception by delta agonists: characterization with antagonists.
The functional interactions between supraspinal mu and delta receptors were characterized in the mouse using mu receptor-selective antagonists. The effects of pretreatment with the mu opioid antagonists, beta-funaltrexamine (beta-FNA) and naloxonazine on the modulation of morphine antinociception by the delta agonists [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2,Met5]enkephalinamide (DAMA) were studied. When co-administered in the same i.c.v. injection, a sub-antinociceptive dose of DPDPE consistently and significantly increased the antinociceptive potency of morphine in control animals, while a sub-effective dose of DAMA decreased morphine antinociception; both the respective increase and the decrease of morphine potency by DPDPE and DAMA had been previously shown to be blocked by ICI 174,864, a delta antagonist. Pretreatment of mice with the non-equilibrium mu antagonist beta-FNA 4 h prior to testing, a pretreatment which had no effect on i.c.v. DPDPE or DAMA antinociception, prevented the modulation of morphine antinociception by both DPDPE and DAMA. Pretreatment with the long acting mu 1 antagonist naloxonazine, 24 h prior to testing, failed to affect the modulation of morphine antinociception by either DPDPE or DAMA; such a pretreatment had no effect on the antinociceptive effects of DPDPE or DAMA when given alone. These results provide further support for the concept of a functionally coupled mu-delta receptor complex which is sensitive to antagonism by beta-FNA, but not naloxonazine, and support the notion that subtypes of opioid mu and delta (i.e. complexed and non-complexed) receptors may exist.
Heyman
J S
JS
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
Jiang
Q
Q
Rothman
R B
RB
Mosberg
H I
HI
Porreca
F
F
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004744:Enkephalin, Methionine; D009271:Naltrexone; C022118:enkephalinamide-Met, Ala(2)-; C024524:beta-funaltrexamine; C034643:naloxonazine; D020881:Enkephalin, D-Penicillamine (2,5)-