Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine.
Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide that is synthesized through the posttranslational processing of beta-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1-100 nmol) or saline (10 microl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1-300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.
Owen
M D
MD
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Unal
C B
CB
Callahan
M F
MF
Trivedi
K
K
York
C
C
Millington
W R
WR
D000138:Acidosis / Q000139:chemically induced; D000698:Analgesia; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000139:chemically induced; D000860:Hypoxia / Q000139:chemically induced; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*
D004151:Dipeptides; C039788:glycylglutamine; D002245:Carbon Dioxide; D009020:Morphine; D010100:Oxygen