title: Derivatives of CCK-(26-32) as cholecystokinin receptor antagonists in guinea pig pancreatic acini.
abstract: In the present study we synthesized cholecystokinin-(26-32)-amide [CCK-(26-32)-NH2], N-acetyl-cholecystokinin-(26-32) [Ac-CCK-(26-32)], and N-acetyl-cholecystokinin-(26-32)-amide [Ac-CCK-(26-32)-NH2]. None of these peptides altered amylase secretion from dispersed acini prepared from guinea pig pancreas, but each peptide inhibited the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin [CCK-(26-33)]. Half-maximal inhibition of CCK-(26-33)-stimulated amylase secretion occurred with 10 microM CCK-(26-32)-NH2, with 25 microM Ac-CCK-(26-32)-NH2, and with 100 microM Ac-CCK-(26-32). Ac-CCK-(26-32) caused a parallel rightward shift in the dose-response curve for CCK-(26-33)-stimulated amylase secretion. Ac-CCK-(26-32)-NH2 inhibited the stimulation of amylase secretion caused by CCK-(26-33), caerulein, or gastrin-(2-17) but did not alter the stimulation caused by carbachol, bombesin, physalaemin, A23187, vasoactive intestinal peptide, secretin, or 8-bromoadenosine 3',5'-cyclic monophosphate. There was a close correlation between the abilities of derivatives of CCK-(26-32) to inhibit binding of 125I-cholecystokinin (125I-CCK) to pancreatic acini and their abilities to inhibit the stimulation of amylase secretion caused by CCK-(26-33). Half-maximal inhibition of binding of 125I-CCK occurred with 5 microM CCK-(26-32)-NH2, with 7 microM Ac-CCK-(26-32)-NH2, and with 70 microM Ac-CCK-(26-32). These findings indicate that each of the three derivatives of CCK-(26-32) is a specific competitive antagonist of the interaction of cholecystokinin with its cell surface receptors on pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011949:Receptors, Cholecystokinin; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; C040529:cholecystokinin (26-32); D000681:Amylases; D012844:Sincalide