Regional Distribution of Cholecystokinin-Like Immunoreactivity in the Human Brain*

Abstract

The concentration of cholecystokinin octapep-tide (CCK-8) was measured by RIA in extracts of seven regions of seven human brains obtained at autopsies of accident, victims. The highest concentrations (picomoles per g tissue; mean ± SE) were found in the amydala (64.1 ± 14.8), frontal cortex (51.6 ± 17), hippocampus (49.8 ± 7.8), and hypothalamus (48.9 ± 10.5), and the lowest concentration was in the cerebellum (0.2 ± 0.03). The brain tissue extracts showed parallelism in RIA with synthetic CCK-8. In another RIA using a specific gastrin antibody, all brain regions contained less than 0.2 pmol gastrin⁄g tissue. On Sephadex G-50 chromatography, the CCK-like immunoreac-tivity from a pool of different human brain regions eluted as a single peak corresponding with CCK-8. On ion exchange chromatography using aminoethyl cellulose (AE-41), the CCK eluted i n a single peak that corresponded with the sulfated octapeptide. On high performance liquid chromatography of the peak from the Sephadex G-50 column, both the brain extract and synthetic CCK-8 eluted in two peaks. To examine possible effects of temperature and time lapse between death and the extraction procedure on the brain CCK levels, rats were sacrificed with ether; the brains were removed and extracted immediately, or extracted after the bodies had remained for 2, 8, or 24 h at either 4 or 23 C. There were no significant differences in the mean brain CCK concentrations of these groups. On Sephadex G-50, the immunoreactivity coeluted with CCK-8. These data suggest that there is no loss of CCK content for 24 h after death and provide evidence that the CCK concentrations in the human brains are not seriously affected in the immediate postmortem state. The wide distribution and regional localization of CCK-8 in the human brain suggest a physiological role for this peptide.