Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas.
The effects of proteinase inhibitors on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of secretin. Each drug tested was administered i.a. Graded doses of gabexate (1-10 mg) elicited dose-dependent biphasic responses for the secretory rates, bicarbonate concentrations and outputs of pancreatic juice, with maximum effects at approximately 5 mg, but had little effect on the protein concentrations. Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration. Secretin (0.03-0.3 U) usually produced similar to gabexate-induced results (1-5 mg). Both bicarbonate and protein concentrations of the juice obtained with gabexate or camostat were almost the same as those obtained with secretin at a similar secretory rate of pancreatic juice, suggesting the secretory action of gabexate or camostat might be similar to that of secretin. In addition, gabexate (3 mg) and camostat (10 mg) elicited more than the respective additive secretory responses in the presence of i.a. infusion of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (12 micrograms/min) as well as secretin (0.1 U). These results indicate that gabexate and camostat induce water and bicarbonate secretion by acting directly on ductular cells of the dog pancreas, which might be mediated at least partially through cyclic AMP.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
A
A
Horiuchi
K
K
Iwatsuki
H
H
Yonekura
L M
LM
Ren
S
S
Chiba
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001550:Benzamidines; D001639:Bicarbonates / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D004285:Dogs; D004952:Esters; D005260:Female; D016670:Gabexate; D006023:Glycoproteins / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D011480:Protease Inhibitors / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology
D001550:Benzamidines; D001639:Bicarbonates; D004952:Esters; D006023:Glycoproteins; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D012633:Secretin; D016670:Gabexate; D007611:Aprotinin; D000242:Cyclic AMP; C028665:urinastatin; D015056:1-Methyl-3-isobutylxanthine; C032855:nafamostat