Cyclic cholecystokinin analogues that are highly selective for rat and guinea pig central cholecystokinin receptors.
Cholecystokinin (CCK) analogues (JMV310, JMV320, JMV328, and JMV332), obtained by side chain to side chain cyclization of a lysine residue in position 28 with a lysine residue in position 31, were found to be highly selective for the brain CCK receptor (CCK-B receptor), both in guinea pig and rat. In these analogues, the C-terminal tetrapeptide region of the molecule, which is the crucial determinant for binding to CCK-B receptors, has been constrained by cyclization. These analogues were highly potent in inhibiting binding of labeled CCK-8 to rat and guinea pig brain membranes (apparent affinity in the nanomolar range) but were poorly efficacious in inhibiting binding of labeled CCK-8 to rat or guinea pig pancreatic acini. In agreement with their low affinity for the pancreatic receptor, these CCK analogues were not very potent in stimulating amylase secretion. These cyclic CCK analogues were demonstrated to be highly selective for the brain CCK receptors.
Centre de Pharmacologie-Endocrinologie, Montpellier, France.
M
M
Rodriguez
M F
MF
Lignon
M C
MC
Galas
M
M
Amblard
J
J
Martinez
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism
D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide