NEUROPEPTIDE-Y INHIBITS POTASSIUM-STIMULATED GLUTAMATE RELEASE THROUGH Y-2 RECEPTORS IN RAT HIPPOCAMPAL SLICES IN-VITRO

1 We investigated the effects of neuropeptide Y (NPY), peptide YY (PYY ), NPY13-36, NPY18-36, [Leu(31)][Pro(34)]NPY and of pancreatic polypep tide Y (PPY) on calcium-dependent, potassium-stimulated glutamate rele ase in superfused rat hippocampal slices. 2 NPY, PYY and the Y-2 recep tor agonist NPY13-36 equipotently inhibited the release of glutamate. The half-maximal response was observed at about 10 nM in a dose-depend ent manner (3 to 100 nM). Maximal inhibition of 50 to 60% was obtained at 100 nM. At higher concentrations of the peptides (300 nM and 1 mu M) this inhibition was partially or entirely reversed. Porcine NPY13-3 6 and NPY18-36 inhibited glutamate release by about 44% at 100 nM. 3 T he specific Y-1 receptor agonist, [Leu(31)][Pro(34)]NPY, caused an ins ignificant increase in glutamate release at 100 to 300 nM concentratio ns. PPY had no effect on potassium-evoked glutamate release in hippoca mpal slices at concentrations of 30 nM to 1 mu M. 4 The experiments su pport previous electrophysiological data. They suggest a potent inhibi tory action of NPY through NPY-Y-2 receptors on the release of the exc itatory amino acid glutamate in rat hippocampus. Especially under cond itions of increased NPY synthesis, such as in epilepsy, this mechanism may be of pathophysiological relevance.