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

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.