Association of neuropeptide YY1 receptors with glutamate-positive and NPY-positive neurons in rat hippocampal cultures

The hippocampus is particularly enriched with neuropeptide tyrosine (NPY) a nd NPY receptors including the Y-1, Y-2 and Y-5 subtypes. We have previousl y reported on the enrichment of cultured rat hippocampal neurons in specifi c [I-125][Leu(31),Pro(34)]PYY/BIBP3226-sensitive (Y-1) binding sites and Y- 1 receptor mRNAs [St-Pierre et al., (1998) Br. J. Pharmacol., 123, p183]. W e have now identified which cell types express the Y-1 receptor. The majori ty of Y-1 receptors, visualized using either the radiolabeled probe [I-125] [Leu(31),Pro(34)]PYY or two antibodies directed against distinct domains of the Y-1 receptor, was expressed in neurons as revealed by neuron-specific enolase (NSE) immunostaining. One antibody was directed against the second extracelllular loop of the Y-1 receptor (amino acids 185-203) whereas the s econd was directed against the intracellular C-terminal loop (amino acids 3 55-382), The labelling was evident over both perikarya and processes. Neuro ns labelled by the various Y-1 receptor probes were mostly glutamate-positi ve as revealed by double immunostaining. Most interestingly, a number of NP Y-positive cultured hippocampal neurons were also enriched with the Y-1 rec eptor, suggesting that this subtype may act as an autoreceptor to regulate NPY release in the hippocampus. These results thus provide an anatomical ba sis for the modulation of glutamate and NPY release by the Y-1 receptor in the hippocampus.