Parish D C, Smyth D G, Normanton J R, Wolstencroft J H
Nature. 1983;306(5940):267-70. doi: 10.1038/306267a0.
The primary mechanism of activation of intracellular prohormones seems to involve proteolytic cleavage at sequences of consecutive basic residues. Thus, all the known biologically active peptides derived from the prohormone of corticotropin and beta-endorphin appear to be excised initially by enzymes with this specificity. The C-terminal peptide, beta-endorphin (1-31), is generated by cleavage at a lysyl arginine sequence and an additional cleavage can give rise to the related peptides, beta-endorphin (1-27) and beta-endorphin (1-26). These derivatives of beta-endorphin are released by an endopeptidase that appears to catalyse cleavage on the carboxyl side of paired lysine residues, followed by the action of a carboxypeptidase B-like enzyme (Fig. 1). The beta-endorphin fragments, beta-endorphin (1-27) and beta-endorphin (1-26), have been isolated from porcine and bovine pituitary but the C-terminal dipeptide, glycyl glutamine, has not been reported previously. Here we describe the isolation of glycyl glutamine from porcine pituitary and present evidence for its presence in sheep brain stem. When applied ionophoretically to brain stem neurones in the rat, the dipeptide exhibited an inhibitory action on cell firing.
细胞内激素原激活的主要机制似乎涉及在连续碱性残基序列处的蛋白水解切割。因此，所有已知的源自促肾上腺皮质激素和β-内啡肽激素原的生物活性肽最初似乎都是由具有这种特异性的酶切除的。C末端肽β-内啡肽（1-31）是通过在赖氨酰精氨酸序列处切割产生的，进一步切割可产生相关肽β-内啡肽（1-27）和β-内啡肽（1-26）。β-内啡肽的这些衍生物由一种内肽酶释放，该内肽酶似乎催化在成对赖氨酸残基的羧基侧进行切割，随后是一种羧肽酶B样酶的作用（图1）。β-内啡肽片段β-内啡肽（1-27）和β-内啡肽（1-26）已从猪和牛垂体中分离出来，但C末端二肽甘氨酰谷氨酰胺此前尚未见报道。在此，我们描述了从猪垂体中分离甘氨酰谷氨酰胺，并提供了其存在于羊脑干中的证据。当将该二肽离子导入大鼠脑干神经元时，它对细胞放电表现出抑制作用。
