Adult carboxypeptidase E-deficient fat/fat mice have a near-total depletion of brain CCK 8 accompanied by a massive accumulation of glycine and arginine extended CCK - Identification of CCK 8 Gly as the immediate precursor of CCK 8 in rodent brain

Cholecystokinin (CCK) amide concentrations were reduced over 85% in all the major brain regions of carboxypeptidase E (Cpe)(fat)/Cpe(fat) mice in comp arison to control mice. Using an radioimmunoassay (RIA) specific for glycin e-extended CCK (CCK Cry), low levels of CCK Gly were detected in control (0 .65 ng/g tissue) and were even lower in Cpefat/Cpe(fat) (0.246 ng/g) mice b rain extracts, After treatment with carboxypeptidase B, the level of CCK Gl y in Cpe(fat)/Cpe(fat) in these brain extracts was elevated to 33.5 ng/g, a bout 51-fold higher than in control. On gel-filtration chromatography and h igh-performance liquid chromatography (HPLC), this material coeluted with C CK 8 Gly, These results demonstrate that CPE is required for the correct pr ocessing of arginine- and glycine-extended CCK in all major regions of the mouse brain. These results support the hypothesis that CCK 8 Gly is the imm ediate precursor of CCK 8 amide in mouse brain, not larger amidated forms l ike CCK 22 or CCK 33.