[N-methylnorleucine-(28,31)]cholecystokinin-(26-33) (SNF 8702) activity at a cloned rat CCKB receptor.
[N-methyl-Nle 28,31)]cholecystokinin-(26-33) (SNF 8702) is a highly selective ligand for the CCKB type of receptor present in the vertebrate central nervous system. Radioligand binding data showing that SNF 8702 binding affinity is reduced by the GTP analog guanylyl-imidodiphosphate suggest that SNF 8702 is an agonist but the ability of SNF 8702 to activate CCKB receptors has not been demonstrated. The present study shows that SNF 8702 is a highly potent agonist at rat CCKB receptors expressed on COS-7 cells and that these receptors are coupled to the mobilization of intracellular calcium. The A50 measured for SNF 8702-induced calcium mobilization (66 pM) is over 6-fold less than that of cholecytstokinin octapeptide (420 pM). Data are also presented showing that SNF 8702 has high binding affinity for these receptors with a Kd value (760 pM) consistent with previous measurements using guinea pig brain tissue preparations.
Pharmacology Department, University of Arizona College of Medicine, Tucson 85724.
R J
RJ
Knapp
E
E
Malatynska
P
P
Peterson
T
T
Zalewska
S
S
Fang
V J
VJ
Hruby
T L
TL
Smith
H I
HI
Yamamura
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis; D008024:Ligands; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011869:Radioligand Assay; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000096:biosynthesis / Q000737:chemistry; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D018076:DNA, Complementary; D008024:Ligands; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C066684:SNF 8702; D012844:Sincalide; D002118:Calcium