In vivo biosynthesis of cholecystokinin in rat cerebral cortex

The biosynthesis of cholecystokinin (CCK) in the cerebral cortex of rats was studied by intracisternal pulse injections of [35S]methionine. The rats were killed with intervals varying from 15 min to 10 h after the injections. Cortical CCK extracted in boiling water and acetic acid was immunoabsorbed using an antiserum specific for the COOH-terminal sequence of CCK. After displacement from the immunoabsorbent by heptadecapeptide gastrin, which contains the same COOH-terminal sequence as CCK, chromatography on Sephadex G-50 columns showed four molecular forms of CCK with elution constants (Kav) of 0.08, 0.50 (corresponding to the tritriacontapeptide amide, CCK-33), 1.10 (corresponding to the COOH-terminal octapeptide amide, CCK-8) and 1.40 (a component which may correspond to the COOH-terminal tetrapeptide of rat CCK). Chasing with methionine demonstrated a biosynthetic pathway from the largest molecular form to the octapeptide-like form. The results indicate that a rapid and extensive synthesis of CCK takes place in the cerebral cortex, and that a precursor relationship exists between CCK-8 and the larger molecular forms of CCK.