Beta-Endorphin-Induced Cardiorespiratory Depression is Inhibited by Glycyl-L-Glutamine, a Dipeptide Derived from Beta-Endorphin Processing. Appendix 1

摘要

Glycyl-L-glutamine (beta-endorphin-(30-31)) is synthesized through the post-translational processing of beta-endorphin-(1-31). Evidence that glycyl-L-glutamine is a prominent end-product of beta endorphin-(1-31) processing in cardioregulatory regions of rat brain prompted us to investigate whether it modulates the cardiorespiratory depression induced by central beta-endorphin-(1-31) injection. As shown previously, beta-endorphin-(1-31) (0.5 nmol) lowered mean arterial pressure (MAP) and heart rate when administered i.c.v. to pentobarbital anesthetized rats. Glycyl-L-glutamine (.3, 0.6, 1.0, and 10.0 nmol) produced a dose-related inhibition of beta-endorphin-(1-31)-induced hypotension, but not bradycardia, when injected i.c.v. 15 min after beta-endorphin-(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 glycyl-L-glutamine was administered to urethane anesthetized rats or when it was injected prior to beta-endorphin-(1-31). Glycyl-L-glutamine also attenuated the respiratory depressant effect of beta-endorphin-(1-31), significantly inhibiting beta-endorphin-(1-31) significantly inhibiting beta-endorphin-(1-31)-induced hypoxia and hypercapnia. Glycyl-L-glutamine (1, 10 or 100 nmol) was inactive when injected alone, however, producing no significant variation from baseline MAP or heart rate values. These results demonstrate that glycyl-L-glutamine inhibits beta-endorphin-(1-31)-induced 7.