Glycyl-L-glutamine antagonizes alpha-MSH-elicited thermogenesis.

The objective of this study was to determine whether glycyl-L-glutamine [beta-endorphin(30-31)] modulates the thermoregulatory actions of alpha-MSH. Microinjection of alpha-MSH (0.06 nmol) into PGE2-responsive thermogenic sites in the medial preoptic area of rats generated a hyperthermic response, inducing a 0.85 +/- 0.19 degrees C rise in colonic temperature (Tc) within 45 min. Coadministration of glycyl-L-glutamine (3.0 nmol) completely blocked the response, maintaining Tc at baseline levels. This was not attributable to glycyl-L-glutamine hydrolysis because coadministration of glycine and glutamine had no effect on alpha-MSH-induced thermogenesis. Glycyl-L-glutamine, injected alone, was similarly without effect. These data indicate that glycyl-L-glutamine inhibits alpha-MSH-induced thermogenesis but is devoid of thermoregulatory activity itself.