Effect of [(CH2NH)4,5]secretin on pancreatic exocrine secretion in guinea pigs and rats.
[psi 4,5]Secretin was shown to be a secretin receptor antagonist that inhibits secretin-stimulated increase in adenosine 3',5'-cyclic monophosphate in isolated pancreatic acini of the guinea pig. To determine whether it inhibits pancreatic exocrine secretion in vivo, we have studied the effect of [psi 4,5]secretin on the pancreatic secretion stimulated by secretin in anesthetized guinea pigs and rats. In basal state, [psi 4,5]secretin given intravenously for 2 or 3 h in varying doses of 1.6-32.7 nmol.kg-1.h-1 dose dependently increased pancreatic secretion of both fluid and bicarbonate during the 1st h, but it returned gradually to basal level within 2 or 3 h. On the other hand, [psi 4,5]secretin significantly inhibited the pancreatic secretion stimulated by either exogenous or endogenous secretin in a dose-related manner. The inhibitory effect of [psi 4,5]secretin in guinea pigs was greater than that in rats. However, it did not completely block the secretin-stimulated pancreatic secretion, whereas a rabbit antisecretin serum suppressed it completely. We conclude that 1) in the unstimulated state, [psi 4,5]secretin is a partial agonist of pancreatic exocrine secretion of both fluid and bicarbonate; and 2) when pancreatic secretion is stimulated by secretin, unlike an antisecretin serum, it is a partial inhibitor in intact guinea pigs and rats.
Kim
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University of Rochester School of Medicine and Dentistry, Department of Medicine, Isaac Gordon Center for Digestive Diseases and Nutrition, Genesee Hospital, New York 14607.
Li
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Lee
K Y
KY
Coy
D H
DH
Chey
W Y
WY
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D006168:Guinea Pigs; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits / Q000276:immunology; D051381:Rats; D012633:Secretin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013552:Swine; D013997:Time Factors
C084329:(psi-4,5)-secretin; D007106:Immune Sera; D012633:Secretin; D002217:Carbachol; D002766:Cholecystokinin; D012844:Sincalide