Beta-endorphin-induced cardiorespiratory depression is inhibited by glycyl-L-glutamine, a dipeptide derived from beta-endorphin processing.
Glycyl-L-glutamine (Gly-L-Gln), or beta-endorphin-(30-31) [beta-End-(30-31)], is synthesized through the post-translational processing of beta-End-(1-31). Evidence that gly-L-gln is a prominent end product of beta-End-(1-31) processing in cardioregulatory regions of rat brain prompted us to investigate whether it modulates the cardiorespiratory depression induced by central beta-End-(1-31) injection. As shown previously, beta-End-(1-31) (0.5 nmol) lowered mean arterial pressure (MAP) and HR when administered i.c.v. to pentobarbital-anesthetized rats. Gly-L-gln (0.3, 0.6, 1.0 and 10.0 nmol) produced a dose-related inhibition of beta-End-(1-31)-induced hypotension, but not bradycardia, when injected i.c.v. 15 min after beta-End-(1-31). This effect was not attributable to hydrolysis, because equimolar amounts of L-glycine and L-glutamine were ineffective. A comparable response was observed when gly-L-gln was administered to urethane-anesthetized rats and when it was injected before beta-End-(1-31). Gly-L-gln also attenuated the respiratory depressant effect of beta-End-(1-31), significantly inhibiting beta-End-(1-31)-induced hypoxia and hypercapnia. Gly-L-gln (1, 10 and 100 nmol) was inactive when injected alone, however, and produced no significant variation from base-line MAP or HR values. These results demonstrate that gly-L-gln inhibits beta-End-(1-31)-induced cardiorespiratory depression, consistent with accumulating evidence that gly-L-gln functions as a neuromodulator.
Division of Molecular Biology and Biochemistry, University of Missouri-Kansas City, Missouri.
C B
CB
Unal
M D
MD
Owen
W R
WR
Millington
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000037:antagonists & inhibitors; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D013329:Structure-Activity Relationship; D001615:beta-Endorphin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D004151:Dipeptides; D018377:Neurotransmitter Agents; C039788:glycylglutamine; D009270:Naloxone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin