Differential bile-pancreatic secretory effects of CCK-58 and CCK-8.
In this work, we 1) synthesized rat CCK-58, 2) determined the amounts and forms of rat CCK in whole blood after stimulation of its release by casein, 3) determined the potency of CCK-8 and CCK-58 peptides to displace labeled CCK-8 from CCK(A) and CCK(B) receptors transfected into Chinese hamster ovary (CHO) cells, and 4) examined the biological actions of CCK-8 and rat CCK-58 in an anesthetized rat model. CCK-58 was the only detected endocrine form of CCK in rat blood. Synthetic rat CCK-58 was less potent than CCK-8 for displacing the label from CCK(A) and CCK(B) receptors in transfected CHO cells. However, rat CCK-58 was more potent than CCK-8 for stimulation of pancreatic protein secretion in the anesthetized rat. In addition, CCK-58 but not CCK-8 stimulated fluid secretion in this anesthetized rat model. These data suggest that regions outside the COOH terminus of rat CCK-58 influence the expression of CCK biological activity. The presence of only CCK-58 in the circulation and the fact that its biological activity differs from CCK-8 suggests that CCK-58 deserves scrutiny in other physiological models of CCK activity.
Reeve
Joseph R
JR
CURE Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, and Digestive Diseases Division, University of California Los Angeles School of Medicine, USA. jreeve@ucla.edu
Wu
S Vincent
SV
Keire
David A
DA
Faull
Kym
K
Chew
Peter
P
Solomon
Travis E
TE
Green
Gary M
GM
Coskun
Tamer
T
D000596:Amino Acids / Q000032:analysis; D000681:Amylases / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002364:Caseins / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology*; D006224:Cricetinae; D013058:Mass Spectrometry; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000187:drug effects / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000187:drug effects / Q000378:metabolism; D012844:Sincalide / Q000097:blood / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013431:Sulfates / Q000378:metabolism
D000596:Amino Acids; D002364:Caseins; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D013431:Sulfates; C038823:cholecystokinin 58; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide