Md. Owen et al., Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine, AM J P-REG, 279(5), 2000, pp. R1944-R1948
Citations number
27
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Glycyl-glutamine (Gly-Gln; beta -endorphin(30-31)) is an endogenous dipepti
de that is synthesized through the posttranslational processing of beta -en
dorphin in brain stem regions that control respiration and autonomic functi
on. This study tested the hypothesis that Gly-Gln administration to conscio
us rats will prevent the respiratory depression caused by morphine without
affecting morphine antinociception. Rats were administered Gly-Gln (1-100 n
mol) or saline (10 mul) intracerebroventricularly followed, 5 min later, by
morphine (40 nmol icv). Arterial blood gases and pH were measured immediat
ely before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatmen
t inhibited morphine-induced hypercapnia, hypoxia, and acidosis significant
ly. 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-evo
ked antinociception in the paw withdrawal test. When given alone to otherwi
se untreated animals, Gly-Gln did not affect nociceptive latencies or blood
gas values. These data indicate that Gly-Gln inhibits morphine-induced res
piratory depression without compromising morphine antinociception.