Neuropeptide Y inhibits α-MSH release from rat hypothalamic slices through a pertussis toxin-sensitive G protein

The arcuate nucleus of the hypothalamus contains various types of peptidergic neurons. In particular, two distinct populations of neurosecretory neurons containing neuropeptide Y (NPY)- and α-melanocyte-stimulating hormone (α-MSH)-like immunoreactivity have been identified in the arcuate nucleus. Double-labeling immunocytochemical data have recently shown that NPY-containing fibers make synaptic contacts with proopiomelanocortin (POMC) immunoreactive neurons. We have thus investigated the possible effect of NPY on the release of α-MSH from rat hypothalamic slices in vitro, using the perifusion technique. NPY significantly inhibited KCl-stimulated α-MSH release in a dose-dependent manner. The inhibitory effect of NPY was mimicked by the Y 2 agonist, NPY-(13-36), while the Y 1 agonist, [Leu 31Pro 34]NPY, was devoid of effect. Pretreatment of hypothalamic slices with pertussis toxin (PTX) blocked the inhibitory effect of NPY, suggesting that the action of NPY on POMC neurons is mediated through a PTX-sensitive G protein. These results support the notion that NPY may play a physiological role in the regulation of α-MSH release from hypothalamic neurons.