Structural requirements for action of cholecystokinin on enzyme secretion from pancreatic acini.
Using dispersed acini prepared from guinea pig pancreas, we found that the structural requirements for cholecystokinin-induced stimulation of amylase secretion are the same as those for cholecystokinin-induced desensitization of amylase secretion. 1) The relative potencies with which various C-terminal fragments of cholecystokinin cause stimulation are the same as their relative potencies for causing desensitization. 2) With each fragment tested, desensitization occurs with peptide concentrations that are supramaximal for causing stimulation of amylase secretion. 3) Fragments of cholecystokinin less efficacious in causing supramaximal inhibition of amylase secretion are also less efficacious in causing desensitization of amylase secretion. In contrast, there is no obvious fixed relation between the ability of a cholecystokinin fragment to cause stimulation of enzyme secretion and its ability to cause residual stimulation of enzyme secretion. Cholecystokinin and its C-terminal hexadecapeptide are 25-40% more efficacious than the C-terminal decapeptide, octapeptide, and heptapeptide in causing residual stimulation, and the C-terminal pentapeptide and tetrapeptide caused no detectable residual stimulation. The C-terminal tetrapeptide, however, can prevent as well as reverse the residual stimulation caused by other cholecystokinin fragments, and the ability of the tetrapeptide to prevent cholecystokinin-induced residual stimulation is itself fully reversible.
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship
D002766:Cholecystokinin; D000681:Amylases