Carbon tetrachloride-induced eicosanoid synthesis and enzyme release from rat peritoneal leucocytes.
When rat peritoneal leucocytes were incubated with carbon tetrachloride, a PLA2 was activated, eicosanoids were generated and lysosomal and cytoplasmic enzymes were released. The predominant eicosanoid generated was TXB2 with lesser amounts of PGE2, 6-keto PGF1 alpha and LTB4. Preincubation of the cells with two structurally unrelated thromboxane synthetase inhibitors reduced PLA2 activity and enzyme release and also reduced the total amounts of eicosanoids liberated. An anti-PGI2 antibody partially reversed the effects of thromboxane synthetase inhibitors indicating a role for endogenous PGI2 generation in the cytoprotective effects of these agents in this system. Exogenous PGI2 was also cytoprotective but the timing of its administration was critical. The cytoprotective effect of PGI2 was potentiated by a phosphodiesterase inhibitor, indicating a possible pivotal role of cAMP in cell protection.
Lynch
T J
TJ
Blackwell
G J
GJ
Moncada
S
S
D000818:Animals; D001201:Ascites; D002118:Calcium / Q000502:physiology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D011464:Epoprostenol / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D007093:Imidazoles; D011453:Prostaglandins; D013931:Thromboxanes; D007975:Leukotriene B4; C017062:1-benzylimidazole; D013929:Thromboxane B2; D002251:Carbon Tetrachloride; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D005966:Glucuronidase; D002118:Calcium