Chloroquine inhibition of cholera toxin.
Cholera toxin (CT) stimulated adenylate cyclase and a phospholipase which elevated cellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and arachidonic acid (AA). The AA was quickly converted to prostaglandins (PGs) via the cyclo-oxygenase pathway. Chloroquine exerted minimal inhibition of cAMP levels in CT-treated cells, although CT-induced release of [3H]AA and PGs was blocked completely when the drug was added in concentrations as low as 0.1 mM (50 micrograms/ml). Inhibition of [3H]AA release was complete when chloroquine was added before or within 30 min after CT. The capacity of chloroquine to inhibit either phospholipase C (PLC) or phospholipase A2 (PLA2) could explain the antisecretory activity of this drug.
Liang
Y F
YF
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Peterson
J W
JW
Jackson
C A
CA
Reitmeyer
J C
JC
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology*; D002772:Cholera Toxin / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008264:Macrophages; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism*; D013997:Time Factors
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D002738:Chloroquine; D002772:Cholera Toxin; D000242:Cyclic AMP