ABSTRACT
The incubation of isolated rat pancreatic acini with low doses (1 x 10(-11)-1 x 10(-10) M) of cholecystokinin-octapeptide (CCK8) induced amylase release. This CCK8-induced amylase release has been shown to be mediated through the protein kinase C activation and the Ca2+ mobilization which are linked to the phospholipase C-mediated hydrolysis of phosphoinositides. However, the incubation of the acini with high doses (1 x 10(-9)-1 x 10(-7) M) of CCK8 reduced amylase release to the level less than that induced by the maximally effective dose (1 x 10(-10) M) of this secretagogue. Under the same conditions, the high doses of this secretagogue did not inhibit the phospholipase C-mediated hydrolysis of phosphoinositides. The stimulatory action of the maximally effective dose of CCK8 in amylase release was mimicked by the simultaneous addition of protein kinase C-activating 12-O-tetradecanoylphorbol-13-acetate (TPA) and Ca2+ ionophore A23187. A high dose (1 x 10(-7) M) of CCK8 reduced the amylase release induced by the combination of TPA and A23187. These results suggest that the high doses of CCK8 inhibit the secretory process post to the protein kinase C-Ca2+ systems and thereby reduce the amylase release induced by the maximally effective dose of CCK8 in rat pancreatic acini.
Subject(s)
Amylases/metabolism , Calcium/physiology , Pancreas/enzymology , Protein Kinase C/metabolism , Sincalide/pharmacology , Animals , Calcimycin/pharmacology , Drug Synergism , In Vitro Techniques , Male , Pancreas/drug effects , Phosphatidylinositols/metabolism , Rats , Rats, Inbred Strains , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
An epidemiological study on pancreatic cancer was performed, using for evaluation reports from the Ministry of Public Welfare and the National Pancreatic Cancer Registration Committee and cases experienced at the First Department of Surgery in Kobe University Hospital. The incidence of pancreatic cancer was found to have increased over the lost few decades. Aged subjects with family histories of malignant diseases and cases having past histories of chronic pancreatitis were affiliated with the high-risk group for this disease. Cigarette smoking and beverage consumption were also shown to be increased risk factors for pancreatic cancer. Poor results obtainable with the types of treatment presently available for pancreatic cancer indicated the clinical significance of applying screening methods for subjects in the high-risk group.