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)/pancreatic polypeptide (PP) family on synaptic transmission in the arcuate nucleus in rat hypothalamic slices. Application of NPY produced two effects. In some cells NPY produced an outward current that had the properties of a K⁺ current. NPY also inhibited the evoked glutamatergic EPSC recorded in these arcuate neurons by a presynaptic mechanism. Although the effects of NPY on the K⁺ current reversed within a few minutes of washout of the peptide, its effects on the EPSC frequently were longer lasting (>30 min). Similar effects were observed using peptide YY or the NPY analog [Leu³¹,Pro³⁴]NPY. Although K⁺ current activation by [Leu³¹,Pro³⁴]NPY was blocked by the selective Y1 antagonist BIBP 3226, inhibition of the EPSC was blocked only partially. Other NPY-related peptides such as NPY(13-36), PP, and [D-Trp³²]NPY also inhibited the EPSC. However, none of these peptides produced activation of the K⁺ current. Thus, activation of more than one NPY receptor produces synaptic inhibition in the arcuate nucleus. A Y1 receptor activates a K⁺ current postsynaptically, and several receptor types appear to inhibit the EPSC by a presynaptic mechanism.