Endogenous glutamate stimulates release of α-melanocyte-stimulating hormone from the rat hypothalamus

Abstract

Release of α-melanocyte-stimulating hormone (α-MSH) and glutamic acid was quantified from superfused slices of rat hypothalamus. Application of L-glutamic acid 10 −4 M failed to evoke release of α-MSH but, in the presence of 10 −4 M dihydrokainic acid (DHK) an inhibitor of glutamate uptake systems, caused significant stimulation of release. DHK caused gradual and sustained increases in both α-MSH and glutamate release. That in α-MSH was blocked by 10 −4 M DL-2-amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartic acid (NMDA)-type glutamate receptor antagonist. We conclude that hypothalamic glutamate is subject to rapid uptake through mechanisms blocked by DHK and that α-MSH release is stimulated by endogenous and exogenous glutamate through NMDA-type receptors.