Modulation of l-arginine transport and nitric oxide production by gabexate mesylate

Abstract

Gabexate mesylate, a non-antigenic synthetic inhibitor of trypsin-like serine proteinases, is a drug used efficiently in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for haemodialysis. Considering the structural similarity between l-arginine and gabexate mesylate, the effect of this drug on l-arginine transport, nitric oxide (NO) formation and constitutive NO synthase activity in human platelets was investigated. Data have shown that gabexate mesylate inhibited competitively l-arginine uptake by increasing the K m value from 22±2 to 86±6 μM. The K i value was 158 μM at pH 7.4 and 37°. Furthermore, gabexate mesylate decreased dose and time-dependent nitrite and nitrate formation (NO x release) and cGMP accumulation in whole cells. In addition, gabexate mesylate inhibited constitutive nitric oxide synthase in a cell-free extract. We concluded that gabexate mesylate could be considered an effective modulator of cellular NO synthesis.