Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.
In this paper, cholecystokinin (CCK) B-type binding sites were characterized with receptor binding studies in different human brain regions (various parts of cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellar cortex) collected from 22 human postmortem brains. With the exception of the thalamus, where no specific CCK binding sites were found, a pharmacological characterization demonstrated a single class of high affinity CCK sites in all brain areas investigated. Receptor densities ranged from 0.5 fmol/mg protein (hippocampus) to 8.4 fmol/mg protein (nucleus caudatus). These CCK binding sites displayed a typical CCKA binding profile as shown in competition studies by using different CCK-related compounds and non peptide CCK antagonists discriminating between CCKA and CCKB sites. The rank order of agonist or antagonist potency in inhibiting specific sulphated [propionyl-3H]cholecystokinin octapeptide binding was similar and highly correlated for the brain regions investigated as demonstrated by a computer-assisted analysis. Therefore it is concluded that CCKB binding sites in human cerebral cortex, basal ganglia, cerebellar cortex share identical ligand binding characteristics.
Institute of Pharmacology and Toxicology, Medical faculty (Chartié), Humboldt University of Berlin, Germany.
S
S
Kinze
T
T
Schöneberg
R
R
Meyer
H
H
Martin
R
R
Kaufmann
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002525:Cerebellar Cortex / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects
D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin