Comparison of CCK-8 receptors in the pancreas and brain of rats using CCK-8 analogues.
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, Kd, of 0.76 nM and a maximum number of specific binding sites, Bmax, of 271.91 fmol/mg protein. On the other hand, the CCK receptor in the cerebral cortex had a Kd of 1.66 nM and a Bmax 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 greater than CCK-7 = SucCCK-7 greater than Suc[Sar3]CCK-7 greater than Suc[D-Trp3]CCK-7 greater than Suc[D-Ala3]CCK-7 greater than [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.
Takeda
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Hoshino
M
M
Yanaihara
N
N
Yanaihara
C
C
Isobe
J
J
Sugiura
N
N
Kashimoto
K
K
Takano
Y
Y
Kamiya
H
H
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology*
D011506:Proteins; D011949:Receptors, Cholecystokinin; D012844:Sincalide