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Procholecystokinin processing in rat cerebral cortex during development.

N W Mogensen¹, L Hilsted, L Bardram

¹Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen, Denmark.

Brain Research. Developmental Brain Research

|June 1, 1990

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The brain expresses procholecystokinin (proCCK) early, but bioactive CCK peptides mature later. Post-translational processing, not gene expression, primarily regulates CCK peptide levels in the brain.

Area of Science:

Neuroscience
Molecular Biology
Biochemistry

Background:

The neuropeptide cholecystokinin (CCK) plays crucial roles in the central nervous system.
Understanding the developmental regulation of CCK is essential for deciphering its functions.

Purpose of the Study:

To investigate the post-translational processing of procholecystokinin (proCCK) in the developing rat cerebral cortex.
To determine the developmental timeline of CCK peptide maturation from fetal to adult stages.

Main Methods:

Utilized a library of radioimmunoassays specific to proCCK sequences.
Analyzed proCCK and processed CCK peptide concentrations in rat cerebral cortex at various developmental time points (fetal, postnatal days 7, 21, and adult).
Employed gel chromatography to assess C-terminal processing intermediates.

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Main Results:

ProCCK was detected in the fetal cortex and remained constant until postnatal day 21, then declined.
Bioactive, alpha-carboxyamidated CCK levels increased significantly from fetal stages to adulthood, with a steep rise between postnatal days 7 and 21.
Glycine-extended intermediates showed a gradual increase throughout development.
Gel chromatography confirmed variable C-terminal processing during development.

Conclusions:

The CCK gene is transcribed into proCCK early in fetal brain development.
The maturation of bioactive CCK peptides is primarily regulated by post-translational modifications, not transcriptional control.
CCK peptide processing is a dynamic developmental process in the rat cerebral cortex.