Repeated intragastric instillation of camostat, a synthetic protease inhibitor, to rats resulted in pancreatinc hypertrophy and hyperplasia. This effect is probably due to the trophic action of increased circulating levels of endogenous CCK on
the
pancreas. The function of exocrine pancreas and regulated mainly by cholinergic nerve and GI polypeptides, but the role of cholinergic nervous system is not clearly understood. The present study was undertaken to analyze the camostat-induced
secretory
pattern of pancreatic enzymes. Further, the mechanism of the effect of camostat was examined in relation to cholecystokinin (CCK) and cholinergic pathway.
Male Sprague-Dawley rats were treated with camostat (200 mg/kg, i. g., Ono pharmaceutical Co., Japan; Ilsung pharmaceutical Co., Korea), in combination with CCK receptor antagonist L364.718 (1 mg/kg, i. g., kindly supplied by Dr. VJ Lotti, Merk
Sharp &
Dome Research Lab., West Point, PA, USA) or cholinergic receptor antagonist atropine (5 mg/kg, i.p.) for 4 days. The secretion of individual enzyme was analyzed by HPLC using TSK phenyl 5PW hydrophobic interaction column. The pancreatic secretion
was
stimulated with secretin (0.5 CU/kg/hr) with or without CCK (CCK-8; 600 ng/kg/hr). The weight of pancreas, tissue enzyme content, and pancreatic secretion of luid and protein were increased in camostat-treated rats. These effects were completely
abolished by L3 4,718, but rather augmented by atropine. Atropine treatment itself resulted in increase of the weight of pancreas. HPLC chromatogram showed that camostat treatment caused increase of proteases fractions, especially the serine
proteases.
L364,718 blocked these camostat-induced changes but atropine did not.
Above results suggest that camostat induces hypertrophy of pancreas and increases in proteases secretion, and these changes are mostly via endogenous CCK release, and cholinergic nerve may have inhibitory effect on CCK release.
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