Orexin-A-induced feeding is dependent on nitric oxide.
Orexin-A is a peptide produced in the lateral hypothalamus/perifornical area, which stimulates feeding. The production of orexin-A is determined by the metabolic state of the animal. We have previously shown that nitric oxide (NO) plays an important role as a mediator of feeding induced by a variety of neuropeptides. This raises the question of whether orexin-A's effects are NO dependent. Here, we first determined that intracerebroventricular administration of 25 ng of orexin-A significantly increased food intake in satiated mice. We next examined the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on orexin-A-induced increase in food intake. L-NAME (50 mg/kg; SC) significantly blocked the orexin-A-induced increase in food intake. Orexin-A administration increased the levels of nitric oxide synthase in the hypothalamus. To further verify the importance of NO in the orexin-A-induced increase in food intake, we compared the ability of orexin-A to increase food intake in neuronal nitric oxide synthase knockout (NOS-KO) mice and their wild-type controls. Orexin-A failed to increase food intake in the NOS-KO mice, whereas it did increase food intake in the wild-type controls. This supports the hypothesis that nitric oxide is a central regulator of food consumption.
Farr
Susan A
SA
Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, and Department of Internal Medicine, Division of Geriatric Medicine, St. Louis University School of Medicine, St. Louis, MO 63106, USA. farrsa52@aol.com
Banks
William A
WA
Kumar
Vijaya B
VB
Morley
John E
JE
D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D000068797:Orexins
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D019331:NG-Nitroarginine Methyl Ester