Regulation of neuropeptide Y release from hypothalamic slices by melanocortin-4 agonists and leptin

We have examined the regulation of the orexigenic neurotransmitter, NPY, in hypothalamic slices of rat brain to discover whether the leptin or melanoc ortin receptor-4 (MCR-4) agonists, which act as satiety signals, can influe nce the release of this neurotransmitter. Basal and potassium-stimulated NP Y release from hypothalamic slices was not significantly altered by the add ition of recombinant murine leptin. However, the melanocortin-4 agonists, a lpha-MSH and MT-II, significantly inhibited potassium-stimulated NPY releas e (p < 0.01) without significantly altering basal NPY release. However, the MCR-4 antagonist, agouti-related protein, did not significantly alter eith er basal or stimulated NPY release. In conclusion, hypothalamic NPY release can be attenuated by MCR-4 agonists, but not by leptin, suggesting that th e activation of MCR-4 receptors leading to satiety can also Further inhibit food intake through an inhibition of orexigenic NPYergic activity. (C) 200 0 Elsevier Science Inc. All rights reserved.