Comparison of CCK-8 Receptors in the Pancreas and Brain of Rats Using CCK-8 Analogues

Abstract

The characteristics of cholecystokinin (CCK) receptors in rat pancreatic acini and in various regions of the brain were examined using synthetic CCK-8 or CCK-7 analogues. ³H-propionylated CCK-8 ([³H]CCK-8) was used as a ligand. 1) The pancreatic CCK receptor had a single high affinity binding component with a dissociation constant, K_d, of 0.76 nM and a maximum number of specific binding sites, B_maX, of 271.91 fmol/mg protein. On the other hand, the CCK receptor in the cerebral cortex had a K_d of 1.66 nM and a B_maX of 30.15 fmol/mg protein. 2) The order of the potencies of CCK-7 and CCK-8 analogues with a substitution at position 3 or 4 to displace [³H]CCK-8 specific binding to the pancreatic acini was as follows: CCK-8>CCK-7=SucCCK-7>Suc[Sar³]CCK-7>Suc[D-Trp³]CCK-7 >Suc[D-Ala³]CCK-7>[D-Trp⁴]CCK-8=[D-Ala⁴]CCK-8. This order of potencies of CCK analogues was greatly different from that in the cerebral cortex. 3) The carboxy-terminal tetra-peptide (CCK-4) and penta-peptide (CCK-5) had very weak potencies in displacing [³H]CCK-8 binding in the pancreatic acini, which were 20 to 30-fold less than their potencies in the cerebral cortex. These results suggest that the recognition sites for CCK analogues in the pancreatic and brain CCK receptors are different.