Inhibitory Effects of ω-Guanidino Acid Esters on Trypsin, Plasmin, Thrombin and Plasma Kallikrein

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation

“…Mice fed raw soya flour for 18 months had an enlarged pancreas but were relatively resistant to the carcinogenic effects of azaserine, whereas hamsters fed such diets for 15 months did not exhibit pancreatic enlargement and had a low tumour incidence (< 10%) after exposure to BOP (Liener & Hasdi, 1986). Pancreatic contents of DNA, RNA and protein were unchanged by feeding raw soya flour to monkeys and were almost unchanged in pigs (Struthers et al, 1983). (2) Synthetic (camostate) Camostate, a synthetic guanidino acid ester, is a potent inhibitor of several enzymes: trypsin, kallikrein, plasmin, thrombin, complement protein (CI) esterase and phospholipase A2 (Muramatu & Fujii, 1972;Tamura et al, 1977;Freise et al, 1983). Like soybean trypsin inhibitor, camostate will increase circulating CCK concentrations and stimulate pancreatic growth in rats when added to the diet (Goke et al, 1986;Otsuki et al, 1987;Wisner et al, 1988;Douglas et al, 1989;Douglas et al, 1990b (Wisner et al, 1988;Douglas et al, 1989;Douglas et al, 1990b).…”

An α2-Macroglobulin Inhibitor, API-13782, Produced byStreptomyces canusOFR-1267

“…The residual activity of Cis was measured with ATEe as a substrate according to the method of Muramatsu et al 14 ) The esterolytic activity of Cis was inhibited by API-13782 at high concentration, therefore antil-CT inactivator activity was calculated by subtracting the anti-Cis activity.…”

“…The proteases tested were preincubated with API-13782 at 37°C for 10 min, then the residual activities were determined by the caseinolytic method for cx-chymotrypsin, the protaminolytic method for trypsin and plasmin as described above, the clotting method for thrombin,15) the chromogenic substrate method for kallikrein and urokinase according to the manufacture's instructions, and the esterolytic method for Cis. 14) The residual activity of pepsiu was determined with hemoglobin as a substrate. 16 ) The percentage inhibition was calculated as (100-a), where a was the activity of the protease with API-l 3782 shown as a percentage of that without API-13782.…”

Novel Trial for the Treatment of Steroid Dependency in Minimal Change Disease: Combined Therapy of Camostat Mesilate and Glycyrrhizin

“…We have previously described the antiproteinuric effects of an oral protease inhibitor, camostat mesilate, in patients with persistent proteinuria due to various nephropathies [6]. This medicine has been developed in Japan [7] and is now used for the treatment of chronic pancreatitis [8,9]. Although the precise mechanisms are still unknown, an anticoagulant effect is considered to be associated with the antiproteinuric effect of this medicine [10].…”