Glycyl glutamine, an inhibitory neuropeptide derived from β-endorphin

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Abstract
The primary mechanism of activation of intracellular prohormones seems to involve proteolytic cleavage at sequences of consecutive basic residues1. Thus, all the known biologically active peptides derived from the prohormone of corticotropin and β-endorphin appear to be excised initially by enzymes with this specificity. The C-terminal peptide, β-endorphin (1–31), is generated by cleavage at a lysyl arginine sequence and an additional cleavage can give rise to the related peptides, β-endorphin (1–27) and β-endorphin (1–26). These derivatives of β-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 β-endorphin fragments, β-endorphin (1–27) and β-endorphin (1–26), have been isolated from porcine2–4 and bovine pituitary5 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.