Mason R T, Peterfreund R A, Sawchenko P E, Corrigan A Z, Rivier J E, Vale W W
Nature. 1984;308(5960):653-5. doi: 10.1038/308653a0.
Calcitonin gene-related peptide (CGRP) is a putative novel neuropeptide predicted on the basis of alternative RNA processing events of primary transcripts of the calcitonin gene. Distinct mRNAs encoding either calcitonin or CGRP are generated from the calcitonin gene RNA transcript in what appears to be a tissue-specific manner. The predicted peptide has now been detected immunocytochemically in discrete regions of the central and peripheral nervous systems and potent in vivo actions have been reported for centrally and peripherally administered synthetic CGRP. However, so far there is no evidence that CGRP is secreted or released by intact cells. The present experiments investigated the possible secretion of CGRP in vitro using primary dispersed cell cultures of the adult rat trigeminal ganglion, which previously has been found to contain large amounts of CGRP mRNA (ref. 2). We report here that immunoreactive CGRP is spontaneously released by cultured trigeminal ganglion cells and that secretion is stimulated by incubation in high potassium medium in a calcium-dependent fashion. Chromatographic characterization of the secreted CGRP-like immunoreactivity (CGRP-LI) isolated only one molecular form which appears to be similar or identical to the predicted rat CGRP (1-37).
降钙素基因相关肽(CGRP)是一种基于降钙素基因初级转录本的可变RNA加工事件预测出的新型神经肽。编码降钙素或CGRP的不同mRNA以组织特异性方式从降钙素基因RNA转录本产生。现在已通过免疫细胞化学方法在中枢和外周神经系统的离散区域检测到预测的肽,并且已报道中枢和外周给予合成CGRP具有强大的体内作用。然而,到目前为止,没有证据表明CGRP是由完整细胞分泌或释放的。本实验使用成年大鼠三叉神经节的原代分散细胞培养物研究了体外CGRP的可能分泌情况,此前已发现该培养物含有大量CGRP mRNA(参考文献2)。我们在此报告,培养的三叉神经节细胞可自发释放免疫反应性CGRP,并且在高钾培养基中孵育时,分泌以钙依赖方式受到刺激。对分泌的CGRP样免疫反应性(CGRP-LI)的色谱分析仅分离出一种分子形式,其似乎与预测的大鼠CGRP(1-37)相似或相同。