Pancreatic secretion in the rat influenced by the low molecular weight serine proteinase inhibitor Gabexate mesilate

Abstract

The effect of intravenous or intragastric administration of the synthetic proteinase inhibitor Gabexate mesilate (GM) on the pancreas of rats was investigated. Infused intravenously at 4 mg kg-1 h-1, GM inhibited both basal or cerulein (0.2 microgram kg-1 h-1)-stimulated pancreatic protein secretion. Intracellular transport and secretion of newly synthesized pancreatic enzymes was not influenced by intravenous infusion of GM. Intragastric administration of GM (400 mg kg-1) on four consecutive days increased pancreatic wet weight, protein and enzyme content of the gland. A preferential increase of proteinases above glucosidases was observed. Pancreatic lobules from inhibitor-treated rats released 30% less amylase in response to cerulein or carbachol when the rate of discharge was expressed in percent of initial content. Expressed in ku amylase/microgram DNA secretion rate was two-fold higher than in controls. In pancreatic duct cannulated rats GM (400 mg kg-1 h-1), introduced intragastrically on five consecutive days, stimulated volume-bicarbonate and protein secretion rate, the secretory response on the fifth day being significantly higher than on the first day. Enzyme pattern in pancreatic juice changed characteristically: mainly the amount of acidic proteinases increased, whereas the amount of the basic isoforms was altered only slightly.