Showing papers on "Orexin-A published in 1999"
TL;DR: It is proposed that orexin regulates sleep/wakefulness states, and that Orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.
2,935 citations
TL;DR: It is determined that canine narcolepsy is caused by disruption of the hypocretin (orexin) receptor 2 gene (Hcrtr2) and this result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for Narcoleptic patients.
2,450 citations
TL;DR: It is shown that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexIn A increases cell firing of intrinsic noradrenergic neurones and modulates neuroendocrine function.
Abstract: The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an important role in orchestrating the sleep-wake cycle.
1,154 citations
TL;DR: A further study of the distribution of ORX-containing neurons in the adult rat brain to provide a general overview of the ORX neuronal system was conducted in this article. But, the results were limited to the lateral hypothalamic area (LHA) and dorsomedial hypothalamic nucleus (DMH), the regions classically implicated in feeding behavior.
1,020 citations
TL;DR: Findings demonstrate that orexin A receptive sites for stimulation of food intake exist primarily in a narrow band of neural tissue within the hypothalamus that is known to be involved in control of energy homeostasis.
325 citations
TL;DR: Orexin A and orexin B were microinjected into the perifornical hypothalamus, lateral hypothalamus (LH), hypothalamic paraventricular nucleus (PVN), and ventral tegmental area (VTA) of male Sprague-Dawley rats to stimulate feeding.
319 citations
TL;DR: The results suggest that orexin may be involved in the regulation of several other behavioral activities in rats, besides feeding.
319 citations
Journal Article•
TL;DR: Orexin A rapidly crosses the BBB from blood to reach brain tissue by the process of simple diffusion, although orexin B is rapidly metabolized in blood and has low lipophilicity.
Abstract: We determined the ability of orexin A and orexin B, recently discovered endogenous appetite enhancers, to cross the blood-brain barrier (BBB) of mice. Multiple time-regression analysis showed that an i.v. bolus of 125I-orexin A rapidly entered the brain from the blood, with an influx rate (Ki = 2.5 +/- 0.3 x 10(-4) ml/g.min) many times faster than that of the 99mTc-albumin control. This relatively rapid rate of entry was not reduced by administration of excess orexin A (or leptin) or by fasting for 22 h, even when penetration into only the hypothalamus was measured. Lack of saturability also was shown by perfusion in blood-free buffer. HPLC revealed that most of the injected 125I-orexin A reached the brain as intact peptide. Capillary depletion studies showed that the administered peptide did not remain bound to the endothelial cells comprising the BBB but reached the brain parenchyma. Efflux of 125I-orexin A from the brain occurred at the same rate as 99mTc-albumin. The octanol/buffer partition coefficient of 0.232 showed that orexin A was highly lipophilic, whereas the value for orexin B was only 0.030. Orexin B, moreover, was rapidly degraded in blood, so no 125I-orexin B could be detected in intact form in brain when injected peripherally. Thus, although orexin B is rapidly metabolized in blood and has low lipophilicity, orexin A rapidly crosses the BBB from blood to reach brain tissue by the process of simple diffusion.
314 citations
TL;DR: Investigation of the effects of chronic administration of orexin in rats by continuous intracerebroventricular administration by means of an osmotic minipump showed that continuous administration of Orexin-A could not overcome the regulation of energy homeostasis and body weight, however, orexIn-A might be implicated in short-term, immediate regulation of feeding behavior.
217 citations
TL;DR: Orexin cells are strategically sited to contribute to feeding regulation, but their widespread projections suggest that orexins have other physiological roles.
215 citations
TL;DR: It is proposed for the first time that orexin-A may act in the brain to stimulate gastric acid secretion by modulating the vagal system and is a candidate mediator of cephalic phase gastric secretion.
TL;DR: Orexin A has a wide distribution in the CNS, but appetite regulation may not be its main function, and its concentrations in the hypothalamus, inferior and superior colliculi and brainstem are unusual.
TL;DR: As a corollary, orexin A may be released into the ventricles and interact with neurons in distant targets, in addition to influencing the activity of neurons with which ORX-LI axons make synaptic contacts.
TL;DR: Results indicate that orexin peptides are involved in the hypothalamic regulatory pathways of feeding behavior in goldfish and were more potent than Orexin-A in stimulation of both feeding behavior and food intake.
TL;DR: It is demonstrated that a fraction of OrA-ir neurons in the tuberal hypothalamus project to areas of the medulla that are involved in autonomic functions.
TL;DR: The widespread orexin distributions in the nuclei of diencephalon and brainstem suggest that orexins serve as neuromodulators, neurotransmitters, or both, in a wide variety of neural networks that regulate the autonomic and neuroendocrine systems.
TL;DR: The findings suggest that orexin A acts on the hypothalamus to inhibit TRH release, and this action is associated with down-regulation in the secretion of thyrotropin-releasing hormone and thyroid hormone.
Abstract: Effects of orexin A on secretion of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) in rats were studied. Orexin A (50 microg/kg) was injected iv, and the rats were serially decapitated. The effects of orexin A on TRH release from the rat hypothalamus in vitro and on TSH release from the anterior pituitary in vitro were also investigated. TRH and thyroid hormone were measured by individual radioimmunoassays. TSH was determined by the enzyme-immunoassay method. The hypothalamic TRH contents increased significantly after orexin A injection, whereas its plasma concentrations tended to decrease, but not significantly. The plasma TSH levels decreased significantly in a dose-related manner with a nadir at 15 min after injection. The plasma thyroid hormone levels showed no changes. TRH release from the rat hypothalamus in vitro was inhibited significantly in a dose-related manner with the addition of orexin A. TSH release from the anterior pituitary in vitro was not affected with the addition of orexin A. The findings suggest that orexin A acts on the hypothalamus to inhibit TRH release.
Journal Article•
TL;DR: Orexin A and neuropeptide Y that are known to induce a feeding response when applied centrally, in the present studies also caused hypothermia and appeared to influence thermoregulation via different effector mechanisms.
Abstract: Orexin A and neuropeptide Y that are known to induce a feeding response when applied centrally, in the present studies also caused hypothermia. Neuropeptide Y elicited hypothermia by depressing metabolic rate (without affecting heat loss mechanisms), while orexin A acted through enhancing peripheral heat loss (without affecting metabolic rate). Neither peptide induced coordinated thermoregulatory changes, both of them appeared to influence thermoregulation via different effector mechanisms.
01 Jan 1999