Inhibitory effect of aspirin on cholera toxin-induced phospholipase and cyclo-oxygenase activity.
Cholera toxin (CT) stimulated phospholipase activity and caused [3H]arachidonic acid (3H-AA) release in a murine macrophage/monocyte cell line. Pretreatment of cells with dexamethasone, a phospholipase A2 (PLA2) inhibitor, did not affect CT-induced 3H-AA release. In contrast, aspirin, which is an inhibitor of phospholipase C (PLC), blocked CT-induced 3H-AA release and subsequent prostaglandin (PC) synthesis. The inhibitory effect of aspirin was dose dependent, with 4 mM reducing the CT response by approximately 50%. Similarly, inhibition was time dependent, occurring when the drug was added to the culture medium as late as 30 min after CT. Brief exposure (30 min) of the cells to aspirin did not alter their subsequent response to CT, but 3H-AA release from cells exposed to aspirin for 2.5 h was irreversibly inhibited. The data suggested that CT stimulation of AA metabolism may involve increased PLC activity.
Liang
Y F
YF
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Peterson
J W
JW
Reitmeyer
J C
JC
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D011453:Prostaglandins; D003907:Dexamethasone; D002772:Cholera Toxin; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D001241:Aspirin