The ontogeny of enzymes involved in post-translational processing and metabolism of neuropeptides.
We quantitated the level of activity of several peptidases to determine if enzymes involved in the post-translational processing and metabolism of peptides are detectable and are altered developmentally in specific regions of the rat brain. Carboxypeptidase H (EC 3.4.17.10), a processing enzyme, located in chromaffin secretory granules was expressed at high levels on postnatal day 0 (P 0, birth) in hypothalamus, cortex and cerebellum (3.48, 4.98, 4.29 pmol/mg/min, respectively). An increase of activity occurred from P 0 to P 7 in both hypothalamus and cortex (7.68, 6.94) with a decrease shown in cerebellum (3.89). After P 7, activity increased by P 90 (adult) in the hypothalamus (7.65), decreased to birth levels in the cortex (4.79) and decreased below birth levels in the cerebellum (2.76). This regional pattern of carboxypeptidase H activity may signify its involvement throughout the life of the rat in the synthesis of specific regional neuropeptides important in development. Enzyme activity for the degradative enzymes, neutral endopeptidase (EC 3.4.24.11) and metallo endopeptidase (EC 3.4.24.15) did not present the same developmental pattern as seen with the processing enzyme. Neutral endopeptidase activity doubled in the hypothalamus from P 0 to P 7 (3080 pmol/mg/min) and remained constant throughout the maturation of the animal. In the cortex, activity increased significantly from P 0 to P 30 (1171) and remained at that level to P 90. In the cerebellum, activity decreased from P 0 to P 30 (320) and remained at that level to P 90 (304). At birth, metallo endopeptidase activity was highest in cortex (2702 pmol/mg/min), intermediate in hypothalamus (1658) and lowest in cerebellum (1410).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D009479:Neuropeptides; D002766:Cholecystokinin; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D008666:Metalloendopeptidases; D015260:Neprilysin; C022510:thimet oligopeptidase