Hypothalamic Cocaine- and Amphetamine-Regulated Transcript (CART) and Agouti-Related Protein (AgRP) Neurons Coexpress the NOP1 Receptor and Nociceptin Alters CART and AgRP Release

• DOI: 10.1210/en.2004-1659
• Publication Date: 2005-05-13T00:25:23Z
• Authors: Gavin A. Bewick; Waljit S. Dhillo; Sarah J. Darch; Kevin G. Murphy; James V. Gardiner; Preeti H. Jethwa; Wing May Kong; Mohammed A. Ghatei; Stephen R. Bloom
• Keywords: Nociceptin receptor; Cart; Anorectic; NOP; Orexigenic; Dynorphin

Nociceptin or orphanin FQ (N/OFQ) and its receptor NOP1 are expressed in hypothalamic nuclei involved energy homeostasis. N/OFQ administered by intracerebroventricular arcuate nucleus (ARC) injection increases food intake satiated rats. The mechanisms which unknown. We hypothesized that may regulate neurons containing peptides the control of such as cocaine- amphetamine-regulated transcript (CART), alphaMSH, neuropeptide Y (NPY), agouti-related protein (AgRP). investigated ability to alter release CART, NPY, AgRP using ex vivo medial basal explants. Incubation explants with (1, 10, 100 nM) resulted significant changes CART release. One hundred nanomoles caused a 33% decrease (55-102) immunoreactivity (IR) increased AgRP-IR 163% but produced no change either alphaMSH-IR NPY-IR. Double immunocytochemistry/in situ hybridization demonstrated CART-IR mRNA colocalized throughout hypothalamus, particular paraventricular nucleus, lateral zona incerta, ARC, providing an anatomical basis for action on Dual ARC also express receptor. Our data suggest nociceptin via increase decreasing anorectic peptide increasing orexigenic AgRP.