Inhibition of porcine pancreas phospholipase A2 activation by gabexate mesilate

Abstract

We investigated the effect of gabexate mesilate on the catalytic activity of phospholipase A2 in homogenized porcine pancreatic tissue. Gabexate mesilate is a potent inhibitor of serine proteases. There is no direct inhibition of phospholipase A2 catalytic activity in concentrations up to 6 mmol/l. Preincubation of homogenized pancreatic tissue with gabexate mesilate leads to a reduction of phospholipase A2 activity even in concentrations as low as 6 mumol/l. The activation of purified porcine prophospholipase A2 added to pancreatic tissue can be completely inhibited. Thus gabexate mesilate might influence the activation of phospholipase A2 administered in therapeutic concentrations in inflamed pancreatic tissue.

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice

“…In some experiments, the effect of BR on ACh‐induced contractions was evaluated in the presence of gabexate (a proteolytic enzyme inhibitor, 15 × 10 −6 mol L −1 ), SCH 79797 [a selective protease‐activated receptor‐1 (PAR‐1) antagonist, 15 × 10 −6 mol L −1 ], N 1 ‐3‐methylbutyryl‐ N 4 ‐6‐aminohexanoyl‐piperazine [ENMD‐1068, a selective protease‐activated receptor‐2 (PAR‐2) antagonist, 10 −4 mol L −1 ], rolipram [a selective phosphodiesterase 4 (PDE4) inhibitor, 10 −6 mol L −1 ] and neomycin [a phospholipase C (PLC) inhibitor, 3 × 10 −3 mol L −1 ] (contact time: 20–30 min for each drug). The concentrations of these inhibitors/antagonists were selected on the basis of previous published works 12–15 . The presence of such inhibitors/antagonists did not affect the reproducibility and the stability of the contractions induced by ACh.…”

Continuous regional application of protease inhibitor in the treatment of acute pancreatitis

“…On the other hand, a multicenter controlled study using FOY by the German pancreatitis study group has represented negative results in that no beneficial effects in preventing mortality and complications were achieved even by a high dose (4 g) application of the drug [11]. The German group adopted the dose of 4 g based on previous in vitro evidence [12,13]; however, it remains uncertain whether this dose was enough to achieve its therapeutic tissue concentration. In our experimental study, compared to intravenous application, a regional continuous intra-arterial application led to an approximately 5-times higher concentration of FUT-175 in the pancreas, as is clearly demonstrated in figure 2.…”