Effects of N-(2-hydroxyethyl)nicotinamide nitrate (nicorandil; SG-75) and its derivatives on pancreatic exocrine secretion in the dog.
Nicorandil, a compound containing a nitrate moiety, can act as a K+ channel opener. Previously we reported stimulatory effects of an intraarterial injection of nicorandil on pancreatic exocrine secretion in the isolated, blood-perfused pancreas under a constant perfusion pressure. To clarify this mechanism in relation to the chemical structure we studied the effects of nicorandil and its derivatives [nitrate containing structure, N-(3-hydroxy-propyl)nicotinamide nitrate (SG-89); nitrate lacking structure, N-(2-acetoxyethyl)nicotinamide (SG-209)], in addition to nitroglycerin (TNG) and pinacidil (a potent K+ channel opener) under a constant perfusion flow rate to the pancreas. Nicorandil, SG-89, and TNG elicited a dose-dependent increase in pancreatic fluid secretion, showing increases in bicarbonate and amylase concentrations. In contrast, SG-209 and pinacidil did not stimulate pancreatic secretion. Furthermore, stimulatory action of nicorandil was not inhibited by treatment with an intraarterial infusion of tetraethylammonium (TEA). These results suggest that nicorandil has direct secretory properties on pancreatic exocrine glands and its nitrate moiety has an important role in the stimulation of pancreatic exocrine secretion, but increasing flow rate and K+ channel opening action do not participate in the secretion.
Yonekura
H
H
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Iwatsuki
K
K
Horiuchi
A
A
Chiba
S
S
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D010189:Pancreatic Juice / Q000378:metabolism*; D020110:Pinacidil; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001639:Bicarbonates; D006146:Guanidines; D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; C035663:SG 209; D000681:Amylases; D005996:Nitroglycerin