Inhibitory effect of gabexate mesilate on pancreatic phospholipase A2-mediated hydrolysis of ghost membranes.
Human erythrocyte ghost membranes were incubated with human pancreatic phospholipase A2 [EC 3.1.1.4] in the presence of gabexate mesilate (FOY, ethyl 4-(6-guanidinohexanoyloxy)-benzoate methanesulfonate) in Tris-buffered saline (10 mM Tris-HCl, 150 mM NaCl, 2 mM CaCl2, pH 7.4). Membrane phospholipids were extracted by chloroform-isopropanol, 7:11 (v/v), and separated by thin-layer chromatography. Gabexate mesilate at a concentration of 400 microM caused a 50% inhibition of the enzyme-mediated hydrolysis of membrane phospholipids. When phosphatidylcholine micelles were incubated with the enzyme in the presence of gabexate mesilate, the mode of inhibition of the enzyme action by the drug appeared to be noncompetitive and Ki of gabexate mesilate for phospholipase A2 was 0.77 mM.
D004910:Erythrocyte Membrane / Q000378:metabolism*; D016670:Gabexate; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008823:Micelles; D010179:Pancreas / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000097:blood; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000097:blood; D011458:Prostaglandins E / Q000037:antagonists & inhibitors*
D006146:Guanidines; D008823:Micelles; D010716:Phosphatidylinositols; D010743:Phospholipids; D011458:Prostaglandins E; D016670:Gabexate; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2