Glycyl glutamine, an inhibitory neuropeptide derived from β-endorphin

Abstract

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.

Beta-Endorphin-Induced Cardiorespiratory Depression is Inhibited by Glycyl-L-Glutamine, a Dipeptide Derived from Beta-Endorphin Processing. Appendix 1

“…Glycyl-L-glutamine also produces independent effects unrelated to inhibition of POMC peptides (Parish et al, 1983;Koelle et al, 1988;Lotwick et al, 1990;Haynes, 1991;Nyquist-Battie et al, 1993). This was first demonstrated by Parish et al (1983) who showed that glycyl-L-glutamine reduces the firing rates of brainstem neurons when applied iontophoretically.…”

“…Glycyl-L-glutamine is a major end-product of P-endorphin-(1-31) processing in the brainstem yet its role in cardiovascular regulation has not been previously investigated (Zakarian and Smyth, 1982;Parish et al, 1983). …”

60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective

“…It is significant, however, that the cells that contained C-terminally shortened forms of β-endorphin would also contain glycyl-glutamine released from the C-terminus of the 31-residue peptide (Parish & Smyth 1982). In a related electrophysiological study, Wolstencroft demonstrated that this dipeptide inhibited the firing of brainstem neurons (Parish et al 1983). The possibility should therefore be considered that glycyl-glutamine may act as a low-molecular weight inhibitory messenger regulating neurotransmission.…”

Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

“…A dipeptide, glycyl-glutamine (Gly-Gln; ␤-endorphin 30-31 ), is also produced when ␤-endorphin 1-31 is converted to ␤-endorphin 1-27 (Parish et al, 1983). Glycyl-glutamine is the single most abundant ␤-endorphin-related peptide produced in some brain regions and most peripheral tissues that synthesize POMC, although relatively little is know about its physiological functions (Parish et al, 1983;Smith and Funder, 1988).…”