Centrally mediated opioid induced depression of hepatic glutathione: effects of intracerebroventricular administration of mu, kappa, sigma and delta agonists.
It has recently been demonstrated that morphine produces a loss of hepatocellular glutathione in mice by virtue of its action within the central nervous system. The ability of opioid receptor antagonists to abolish morphine's effect on hepatic glutathione suggests that this action is opioid-receptor mediated. The involvement of opioid receptors in this phenomenon is confirmed in the present study in mice by the ability of naltrexone, 100 micrograms administered intracerebroventricularly (i.c.v.), to completely block the decrease in hepatic glutathione induced by an i.c.v. injection of 100 micrograms of morphine. Intracerebroventricular administration of the selective mu (mu) opioid receptor agonist, (D-Ala2,N-MePhe4,Gly-ol5)enkephalin (DAGO; 25-50 micrograms), or the selective delta (delta) opioid agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE; 3-50 micrograms), like morphine, produced significant decreases in hepatic glutathione 3 h after administration. The selective kappa (kappa) opioid receptor agonists, ethylketocyclazocine (1-30 micrograms) and trans-(+/-)3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide-methane sulfonate (U50 488; 10-300 micrograms), as well as the selective sigma (sigma) opioid agonists, phencyclidine (PCP; 50-300 micrograms) and N-allylnormetazocine (SKF 10,047; 1-30 micrograms), had no effect on the concentrations of glutathione in the liver. It appears from these data that stimulation of mu- or delta-, but not kappa- or sigma-opioid receptors within the central nervous system results in a loss of hepatocellular glutathione.
James
R C
RC
Department of Pharmacology and Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Wessinger
W D
WD
Roberts
S M
SM
Millner
G C
GC
Paule
M G
MG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D007276:Injections, Intraventricular; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000145:classification / Q000187:drug effects*; D013997:Time Factors
D009294:Narcotics; D011957:Receptors, Opioid; D009271:Naltrexone; D009020:Morphine; D005978:Glutathione