Competitive inhibition of nitric oxide synthase by p-aminobenzamidine, a serine proteinase inhibitor

p-Aminobenzamidine competitively inhibits bovine trypsin, human and bovine thrombin, and human plasmin, all of which act on substrates containing preferentially the L-arginyl side chain at their P-1 position, Considering the structural and functional similarity between p-aminobenzamidine and the L-arginyl side chain in trypsin-like serine proteinases, we investigated the interaction of p-aminobenzamidine with mouse brain nitric oxide synthase (NOS), which uses L-arginine as the substrate for generating NO and L-citrulline, p-Aminobenzamidine is a competitive NOS inhibitor (K-i = 1.2 x 10(-4) M, at pH 7.5 and 37.0 degrees C), but not an NO precursor, Therefore, p-aminobenzamidine affects the NO production and the trypsin-like serine proteinase action. (C) 1997 Academic Press.