Cholecystokinin receptors: relationships among phosphoinositide breakdown, amylase release and receptor affinity in pancreas.
The gut hormone cholecystokinin (CCK) octapeptide stimulates the release of amylase from exocrine pancreas, a process believed to be the result of the breakdown of phosphatidylinositol lipids. To examine further the relationship between phosphoinositide (PI) breakdown and amylase release, we have investigated the effect of N-terminally protected CCK C-terminal fragments in these systems using guinea-pig pancreatic lobules. There was a good correlation between the ability of these fragments to elicit amylase release and their potency in enhancing PI breakdown. In general, the EC50 for amylase release is 10-fold lower than the EC50 for PI breakdown. In addition, a good correlation existed between amylase release and the affinity of CCK fragments for [125I]Bolton Hunter-CCK octapeptide binding sites in pancreatic membranes. We also discovered that N-carbobenzyloxy-CCK tetrapeptide was relatively inefficient in causing PI breakdown, but it caused a near maximal stimulation in amylase release. These findings might reflect an amplification mechanism between PI breakdown and amylase release or that N-carbobenzyloxy-CCK tetrapeptide-induced amylase release is independent of PI breakdown.
C W
CW
Lin
B R
BR
Bianchi
D
D
Grant
T
T
Miller
E A
EA
Danaher
M D
MD
Tufano
H
H
Kopecka
A M
AM
Nadzan
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011949:Receptors, Cholecystokinin
D010446:Peptide Fragments; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D000681:Amylases