Glycyl-L-Glutamine: A Dipeptide Neurotransmitter Derived from Beta-Endorphin

摘要

Glycyl-L-glutamine (Gly-L-Gln) is a dipeptide synthesized post-translationallyfrom beta-endorphin. Gly-L-Gln is a major product of beta-endorphin processing in the brainstem, pituitary and several peripheral tissues, but little is known about its physiological function. The long term objective of this research is to characterize Gly-L-Gln's biological activities and test the feasibility of developing pharmacologic agents that mimic or antagonize its effects. This research has achieved five objectives: (1) Demonstrated that Gly-L-Gln is centrally active; it inhibits the hypotension and respiratory depression, but not the analgesia, produced by beta-endorphin; (2) Established the feasibility of developing peripherally active Gly-L-Gln analogs; specifically, we found that cyclo-Gly-L-Gln inhibits morphine and beta-endorphin-induced cardiorespiratory depression when injected peripherally; (3) Demonstrate that Gly-L-Gln produces trophic and neuroimmune effects in peripheral tissues; (4) Developed analytical methods for measuring Gly-L-Gln in biological tissues; and, (5) generated initial evidence that saturable Gly-L-Gln binding sites are present in brain. These data support the hypothesis that Gly-L-Gln functions as a neurotransmitter in brain and a circulating hormone in the periphery. Neurotransmitter, Cardiovascular regulation, RAD IV Glycyl-L-glutamine, Beta-Endorphin, Post-translational processing, Proopiomelanocortin, Peptide.