Mogensen N W, Hilsted L, Bardram L, Rehfeld J F
Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen, Denmark.
Brain Res Dev Brain Res. 1990 Jun 1;54(1):81-6. doi: 10.1016/0165-3806(90)90067-9.
Using a library of radioimmunoassays for essential sequences of procholecystokinin (proCCK), we have examined the post-translational processing in the rat cerebral cortex from fetal to adult state. The concentration of proCCK in the fetal cerebral cortex was 43 +/- 7 pmol/g tissue (wet weight; mean +/- S.E.M. (n = 20)). It remained constant until day 21 post partum, after which it decreased to undetectable levels. In contrast, the concentration of fully processed, bioactive CCK peptides (i.e. alpha-carboxyamidated CCK) rose from 2 +/- 1 pmol/g in the fetal cortex to 122 +/- 21 pmol/g in the adult. A particularly steep increase occurred from day 7 post partum (13 +/- 2 pmol/g) to day 21 (108 +/- 11 pmol/g). The concentration of glycine-extended intermediates rose gradually from 8 +/- 1 pmol/g in the fetal brain to 55 +/- 6 pmol/g in the adult. Gel chromatography of cortical extracts from day 7, 21 and 100 confirmed the variable processing at the C-terminal amidation site. The results show that the CCK gene is expressed as proCCK already in the fetal brain. However, the covalent modifications of proCCK follow different time courses so that only a small fraction reaches maturation until the first week post partum. We conclude that expression of transmitter-active CCK peptides in the brain is largely regulated at the post-translational rather than at the transcriptional level.
利用针对前胆囊收缩素（proCCK）基本序列的放射免疫分析文库，我们研究了大鼠大脑皮层从胎儿期到成年期的翻译后加工过程。胎儿大脑皮层中proCCK的浓度为43±7 pmol/g组织（湿重；平均值±标准误（n = 20））。在产后第21天之前，其浓度保持恒定，之后降至检测不到的水平。相比之下，完全加工的、具有生物活性的CCK肽（即α-羧酰胺化CCK）的浓度从胎儿皮层中的2±1 pmol/g升至成年时的122±21 pmol/g。从产后第7天（13±2 pmol/g）到第21天（108±11 pmol/g）出现了特别急剧的增加。甘氨酸延伸中间体的浓度从胎儿大脑中的8±1 pmol/g逐渐升至成年时的55±6 pmol/g。对第7天、第21天和第100天的皮层提取物进行凝胶色谱分析，证实了C末端酰胺化位点存在可变加工。结果表明，CCK基因在胎儿大脑中就已表达为proCCK。然而，proCCK的共价修饰遵循不同的时间进程，因此直到产后第一周只有一小部分达到成熟。我们得出结论，大脑中具有递质活性的CCK肽的表达在很大程度上是在翻译后而非转录水平受到调控。
