BETA-ENDORPHIN-INDUCED CARDIORESPIRATORY DEPRESSION IS INHIBITED BY GLYCYL-L-GLUTAMINE, A DIPEPTIDE DERIVED FROM BETA-ENDORPHIN PROCESSING

Glycyl-L-glutamine (Gly-L-Gln), or beta-endorphin-(30-31) [beta-End(30 -31)], is synthesized through the post-translational processing of bet a-End-(1-31). Evidence that gly-L-gln is a prominent end product of be ta-End-(1-31) processing in cardioregulatory regions of rat brain prom pted us to investigate whether it modulates the cardiorespiratory depr ession induced by central beta-End-(1-31) injection. As shown previous ly, beta-End-(1-31) (0.5 nmol) lowered mean arterial pressure (MAP) an d HR when administered i.c.v. to pentobarbital-anesthetized rats. Gly- L-gln (0.3, 0.6, 1.0 and 10.0 nmol) produced a dose-related inhibition of beta-End-(1-31)induced hypotension, but not bradycardia, when inje cted i.c.v. 15 min after beta-End-(1-31). This effect was not attribut able to hydrolysis, because equimolar amounts of L-glycine and L-gluta mine were ineffective. A comparable response was observed when gly-L-g ln was administered to urethane-anesthetized rats and when it was inje cted before beta-End-(1-31). Gly-L-gin also attenuated the respiratory depressant effect of beta-End-(1-31), significantly inhibiting beta-E nd-(1-31)-induced hypoxia and hypercapnia. Gly-L-gln (1, 10 and 100 nm ol) was inactive when injected alone, however, and produced no signifi cant variation from base-line MAP or HR values. These results demonstr ate that gly-L-gln inhibits beta-End-(1-31)-induced cardiorespiratory depression, consistent with accumulating evidence that gly-L-gln funct ions as a neuromodulator.