Role of glutamate in regulating hypothalamic proglucagon-derived peptide secretion in vitro

We have previously demonstrated expression of the proglucagon gene and synthesis and secretion of the proglucagon-derived peptides (PGDPs) in the fetal rat hypothalamus. The excitatory amino acid glutamate has been found to be a key regulator of hypothalamic neuroendocrine hormone secretion. Therefore, the effects of glutamate on hypothalamic PGDP secretion and synthesis were examined in the present study, using the hypothalamic culture model. Glutamate (10 microM) significantly stimulated PGDP secretion (P < 0.01), but had no effect on the total PGDP content of the cultures over 24 hr of incubation. Similarly, the metabotropic/ionotropic glutamate receptor agonist, quisqualic acid (10 microM) stimulated PGDP secretion only ( P < 0.05). In contrast, the ionotropic glutamate receptor agonist, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 10 microM) and antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), had no effects on either secretion or content of the hypothalamic PGDPs. These findings suggest that excitatory amino acids, and glutamate in particular, regulate secretion but not synthesis of the PGDPs in the hypothalamus.