Carbobenzoxy amino acids: structural requirements for cholecystokinin receptor antagonist activity.
We used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ-lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain.
Maton
P N
PN
Sutliff
V E
VE
Jensen
R T
RT
Gardner
J D
JD
D000596:Amino Acids / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D005561:Formates / Q000494:pharmacology; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011949:Receptors, Cholecystokinin; D012844:Sincalide / Q000494:pharmacology; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D000596:Amino Acids; D001593:Benzyl Compounds; D005561:Formates; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D007770:L-Lactate Dehydrogenase; D000681:Amylases; D012844:Sincalide