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Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine.

Abstract
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.
AuthorsM D Owen, C B Unal, M F Callahan, K Trivedi, C York, W R Millington
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 279 Issue 5 Pg. R1944-8 (Nov 2000) ISSN: 0363-6119 [Print] United States
PMID11049880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Dipeptides
  • glycylglutamine
  • Carbon Dioxide
  • Morphine
  • Oxygen
Topics
  • Acidosis (chemically induced)
  • Analgesia
  • Animals
  • Carbon Dioxide (blood)
  • Dipeptides (administration & dosage, pharmacology)
  • Hydrogen-Ion Concentration
  • Hypercapnia (chemically induced)
  • Hypoxia (chemically induced)
  • Injections, Intraventricular
  • Male
  • Morphine (administration & dosage, pharmacology)
  • Oxygen (blood)
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley
  • Respiration (drug effects)

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