Hypothalamic orexin-A binding sites are downregulated by chronic nicotine treatment in the rat.
Chronic nicotine treatment (4 mg/kg per day; 14 days) significantly reduced the affinity and density of orexin-A binding sites in the anterior hypothalamus of rat brain. There was a significantly lower sensitivity of orexin-A binding to orexin peptides, to the related secretin and pituitary adenylate cyclase activating peptide, and to unrelated neuropeptide Y (NPY). This change correlated with selective downregulation of a fraction of hypothalamic NPY Y(1) receptors. In previous studies, we have demonstrated an increase in the levels of orexin-A peptide and NPY in discrete hypothalamic areas upon nicotine treatment. This finding contradicts an expected increase in the production of these orexigenic peptides in a model where an inverse relationship is observed between food consumption and nicotine treatment. This study provides a possible explanation to this inconsistency in that a decrease in affinity of orexin-A binding could reduce neural orexin signaling, which may contribute to decreased food intake observed in smokers and animals chronically treated with nicotine.
Kane
J K
JK
Department of Pharmacology, University of Tennessee College of Medicine, 874 Union Avenue, TN 38163, Memphis, USA.
Parker
S L
SL
Li
M D
MD
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D015536:Down-Regulation; D007031:Hypothalamus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D009538:Nicotine