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The effects of DN-9693, a synthesized phosphodiesterase inhibitor, on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas. DN-9693 injected intraarterially caused a dose-dependent increase in the secretion of pancreatic juice and decrease in the perfusion pressure. The threshold doses to increase the pancreatic secretion and to decrease the perfusion pressure were about 100 micrograms and 1 microgram, to decrease the perfusion pressure were about 100 micrograms and 1 micrograms, respectively. Thus, the secretory response was less effective than the vascular response. The secretory activity of DN-9693 (0.3 mg) was approximately equal to that of 0.03 mg of 3-isobutyl-1-methylxanthine, 0.5 mg of papaverine, 5 mg of theophylline, 0.08 0.5 mg of papaverine, 5 mg of theophylline, 0.08 units of secretin and 0.2 units of cholecystokinin. The concentration of bicarbonate in the pancreatic juice induced by DN-9693 was increased, but protein concentration was not. DN-9693-induced pancreatic secretion was not modified by pretreatments with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced pancreatic secretion was significantly potentiated by infusion of DN-9693 (10 micrograms/min), but cholecystokinin-induced one was not. From these results, it is concluded that DN-9693 may produce an increase in pancreatic secretion by acting directly on the pancreatic exocrine gland of the dog, which might be mediated through an increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
June 1986,
Clinical and experimental pharmacology & physiology,
K Iwatsuki, and
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H Yonekura, and
K Haruta, and
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S Chiba
April 1989,
Thrombosis and haemostasis,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
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S Chiba
September 1991,
The Annals of thoracic surgery,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
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S Chiba
August 1987,
Japanese journal of pharmacology,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
January 1986,
Anticancer research,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
September 1994,
Clinical and experimental pharmacology & physiology,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
December 1988,
Japanese journal of pharmacology,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
April 1988,
Thrombosis research,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
October 1985,
Japanese journal of pharmacology,
K Iwatsuki, and
A Horiuchi, and
H Yonekura, and
K Haruta, and
N Homma, and
S Chiba
October 1988,
The Mount Sinai journal of medicine, New York,
