REGULATION OF NEUROTRANSMISSION IN THE ARCUATE NUCLEUS OF THE RAT BY DIFFERENT NEUROPEPTIDE-Y RECEPTORS

We examined the effects of peptides of the neuropeptide Y (NPY)/pancre atic polypeptide (PP) family on synaptic transmission in the arcuate n ucleus in rat hypothalamic slices. Application of NPY produced two eff ects. In some cells NPY produced an outward current that had the prope rties of a K+ current. NPY also inhibited the evoked glutamatergic EPS C recorded in these arcuate neurons by a presynaptic mechanism. Althou gh the effects of NPY on the KC current reversed within a few minutes of washout of the peptide, its effects on the EPSC frequently were lon ger lasting (>30 min). Similar effects were observed using peptide YY or the NPY analog [Leu(31), pro(34)]NPY. Although K+ current activatio n by [Leu(31),pro(34)]NPY was blocked by the selective Y1 antagonist B IBP 3226, inhibition of the EPSC was blocked only partially. Other NPY -related peptides such as NPY(13-36), PP, and [D-Trp(32)]NPY also inhi bited the EPSC. However, none of these peptides produced activation of the K+ current. Thus, activation of more than one NPY receptor produc es synaptic inhibition in the arcuate nucleus. A Y1 receptor activates a K+ current postsynaptically, and several receptor types appear to i nhibit the EPSC by a presynaptic mechanism.