Hepatic and splenic phagocytosis in female B6C3F1 mice implanted with morphine sulfate pellets.
Morphine sulfate has previously been shown to produce a dose-dependent decrease in hepatic phagocytosis when administered as 8-, 25- and 75-mg pellets implanted subcutaneously. This study was undertaken to determine the time course of suppression of hepatic and splenic phagocytosis after subcutaneous implantation of morphine sulfate pellets. Mice were implanted with either 75 mg of morphine sulfate or placebo pellets. The uptake of chromated sheep red blood cells by the liver and spleen was taken as an index of phagocytosis by resident Kupffer cells or macrophages, respectively. The results indicate that maximum suppression of hepatic phagocytosis by 67% occurred 18 hr after implantation of 75 mg of morphine sulfate. Hepatic phagocytic capacity returned to control levels within 48 hr of implantation. The initial time course of suppression of splenic phagocytosis by 41% was similar to that of the liver (maximum at 12 hr). However, splenic phagocytic capacity returned toward placebo levels over a longer period of time reaching control after 4 days after implantation. The opiate receptor antagonist, naltrexone (30-mg pellet), completely blocked the ability of morphine to suppress either hepatic or splenic phagocytosis. Corticosterone is known to increase in parallel with plasma morphine levels presumably through a hypothalamic-pituitary-adrenal axis. The glucocorticoid receptor antagonist RU 486 was used to block the actions of corticosterone and investigate its possible role in morphine sulfate-induced suppression of phagocytosis. RU 486 (200 mg/kg) completely blocked morphine sulfate's ability to suppress splenic phagocytosis. In contrast, RU 486 only partially blocked morphine-induced suppression of hepatic phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Levier
D G
DG
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Brown
R D
RD
McCay
J A
JA
Fuchs
B A
BA
Harris
L S
LS
Munson
A E
AE
D000818:Animals; D004361:Drug Tolerance; D005260:Female; D007728:Kupffer Cells / Q000187:drug effects*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects
D015735:Mifepristone; D009271:Naltrexone; D009020:Morphine