The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulationof prolactin release

In this study, using an enzymatic KPLC method in combination with D-asparta te oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomola r levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its n atural precursor and also occurs as an endogenous compound. Among the endoc rine glands, the highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8 .4 +/- 1.2 nmol/g) occur in the adenohypophysis, whereas the hypothalamus r epresents the area of the nervous system where these amino acids are most a bundant (55 +/- 9 and 5.6 +/- 1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats by ip injection, there is a significant uptake of D-Asp into the adenohypophysis and a significant increase in the concentration of NMDA in the adenohypophysis, hypothalamus and hippocampus , suggesting that D-Asp is an endogenous precursor for NMDA biosynthesis. E xperiments con-ducted on tissue homogenates confirm that D-Asp is the precu rsor of the NMDA and that the enzyme catalyzing this reaction is a methyltr ansferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In vivo experiments consisting of ip injections of sodium D-aspartate show that th is amino acid induced a significant serum PRL elevation and this effect is dose and time dependent. In vitro experiments conducted on isolated adenohy pophysis or adenohypophysis coincubated with the hypothalamus, showed that the release of PRL is caused by a direct action of D-Asp on the pituitary g land and also mediated by the indirect action of NMDA on the hypothalamus. Then, the latter induces the release of a putative factor that in turn stim ulates the adenohypophysis reinforcing the PRL release. Tn conclusion, our data suggest that D-Asp and NMDA are present endogenously in the rat and ar e involved in the modulation of PRL release.