[N-methylnorleucine-(28,31)]cholecystokinin-(26-33) (SNF 8702) activity at a cloned rat CCK_B receptor

[N-methyl-Nle 28,31)]cholecystokinin-(26-33) (SNF 8702) is a highly ligand for the CCK_B 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 CCK_B receptors has not been demonstrated. The present study shows that SNF 8702 is a highly potent agonist at rat CCK_B 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 K_d value (760 pM) consistent with previous measurements using guinea pig brain tissue preparations.