Effects of loxiglumide on pancreatic exocrine secretion stimulated by cholecystokinin-8 in conscious dogs.
The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin-A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by exogenously administered CCK-8 were examined in conscious dogs with chronic pancreatic fistula. Pancreatic exocrine secretion in dogs was significantly increased by intravenous infusion of CCK-8 at a dose of 0.06 microgram/kg/h. Loxiglumide inhibited CCK-8-augmented outputs of pancreatic protein, trypsin and amylase at intravenous doses of 1, 3, 10 mg/kg/h (p < 0.05 or 0.01), and inhibited pancreatic juice volume at a dose of 10 mg/kg/h (p < 0.05). These results demonstrated that the selective CCK-A antagonist loxiglumide inhibited the increase of pancreatic exocrine secretion stimulated by CCK-8 based on selective blockade of receptor binding of CCK in dogs.
Ninomiya
K
K
Pharmacological Research Laboratory, Tokyo Tanabe Co., Ltd., Japan.
Saito
T
T
Wakatsuki
K
K
Saeki
M
M
Kato
T
T
Kasai
H
H
Kimura
K
K
Fujii
M
M
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000378:metabolism
D006727:Hormone Antagonists; D011506:Proteins; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D002766:Cholecystokinin; D000681:Amylases; D014357:Trypsin; D011377:Proglumide