Subject(s)
Eicosanoic Acids/metabolism , Macrophages/metabolism , Morphine Dependence/metabolism , Animals , Male , Rats , Rats, Inbred StrainsABSTRACT
The effect of copper on the release of cyclooxygenase metabolites from starch elicited, rat, peritoneal macrophages was investigated. Copper sulphate, in the range 10(-6)-10(-5) M, inhibited the formation of prostaglandin (PG) E2 and thromboxane (Tx) B2, the stable metabolite of TxA2, in a dose dependent manner but had no effect on the production of 6-keto-PGF1 alpha, the stable product of prostacyclin. At higher concentrations (5 x 10(-5) and 10(-4) M) the synthesis of all three metabolites of arachidonic acid (AA) was stimulated as was the release of radioactivity from macrophages prelabelled with 14C AA. Copper had no effect on the metabolism of exogenous AA however. At 10(-4) M copper also stimulated secretion of the lysosomal enzyme, beta-glucuronidase (GUR). Copper nitrate (10(-4) M), but not zinc sulphate, also stimulated eicosanoid formation and lysosomal enzyme release. Our results are consistent with the idea that copper stimulates eicosanoid formation via an effect on PL activity.
Subject(s)
6-Ketoprostaglandin F1 alpha/metabolism , Copper/pharmacology , Glucuronidase/metabolism , Macrophages/metabolism , Prostaglandin-Endoperoxide Synthases/physiology , Prostaglandins E/metabolism , Thromboxane B2/metabolism , Animals , Arachidonic Acid , Arachidonic Acids/metabolism , Dinoprostone , In Vitro Techniques , L-Lactate Dehydrogenase/metabolism , Lysosomes/enzymology , Male , Phospholipases/metabolism , RatsABSTRACT
Resident peritoneal macrophages from morphine-addicted rats (4 days) released more prostaglandin (PG) E2 and thromboxane (Tx) B2, but not 6-keto-PGF1 alpha, than cells from control animals. This effect, which was due to an enhancement of endogenous AA turnover, was not related to any changes in cAMP synthesis or lysosomal enzyme secretion. [D-Ala2]-Met-enkephalin had no effect on eicosanoid release in vitro. Both morphine and PGE2 have been shown to depress macrophage functions. We suggest that morphine-stimulated macrophage PGE2 synthesis, and the consequent inhibition of phagocytosis, could contribute to the decreased resistance to infections associated with opiate addiction.
Subject(s)
6-Ketoprostaglandin F1 alpha/metabolism , Arachidonic Acids/pharmacology , Macrophages/metabolism , Morphine Dependence/pathology , Morphine/pharmacology , Prostaglandins E/metabolism , Thromboxane B2/metabolism , Animals , Arachidonic Acid , Cells, Cultured , Cyclic AMP/biosynthesis , Dinoprostone , Enkephalin, Methionine/analogs & derivatives , Enkephalin, Methionine/pharmacology , Glucuronidase/metabolism , L-Lactate Dehydrogenase/metabolism , Macrophages/drug effects , Male , Peritoneal Cavity/pathology , Rats , Rats, Inbred StrainsABSTRACT
The basal and carrageenin-stimulated release of thromboxane (TX) B2, the stable product of TXA2, 6-ketoPGF1 alpha, the stable breakdown product of prostacyclin (PGI2) and prostaglandin (PG) E2 from 24 h starch elicited rat peritoneal macrophages was inhibited by dibutyryl-cyclic AMP (db-cAMP). PGE2 also inhibited the release of TXA2 and 6-keto-PGF1 alpha whereas the stable endoperoxide analogue, U-44069, stimulated PGE2 and 6-keto PGF1 alpha release but inhibited TXB2 release. The effects of all three mediators tested were related to an increase of Mø intracellular cAMP content.
