Lowering glucose concentrations increases cytosolic Ca2+ in orexin neurons of the rat lateral hypothalamus

Muroya, Shinji; Uramura, Kazuhide; Sakurai, Takeshi; Takigawa, Morikuni; Yada, Toshihiko

doi:10.1016/s0304-3940(01)02053-5

Cited by 63 publications

(51 citation statements)

References 20 publications

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“…Our results clearly demonstrate the presence of a subset of NPY neurons that serves as the common target for ghrelin and orexin. It has been shown that fasting and lowering glucose concentrations increase the level of ghrelin (9) and activate orexin neurons (26,36), suggesting that the release of the two peptides are regulated in parallel. Our finding indicates that ghrelin and orexin may also cooperate at their common effector site, the NPY neurons in the ARC, which could result in an efficient stimulation of the NPY-mediated neural signaling and feeding.…”

Section: Discussionmentioning

confidence: 99%

“…Adult male Sprague-Dawley (SD) rats were maintained on a 12-h light/dark cycle and given conventional food and water ad libitum. The ARC was isolated from the brain of the 5-to 7-week-old SD rats and then single neurons were prepared according to the procedures reported previously (25,26) with slight modifications. Briefly, rats were anesthetized with an intraperitoneal injection of carbamic acid ethyl ester (900 mg/kg) and decapitated, and their brain was removed.…”

Section: Methodsmentioning

confidence: 99%

“…2؉ ] i in single ARC neurons. At 2-12 h after cell preparation, [Ca 2ϩ ] i was measured by radiometric fura-2 microfluorometry in combination with digital imaging as previously reported (25,26). Briefly, following incubation with 2 mol/l fura-2/AM (Dojin Chemical, Kumamoto, Japan) for 1 h at 18°C, the cells were mounted in a chamber and superfused with HKRB at 1 ml/min at 33°C.…”

Section: Methodsmentioning

confidence: 99%

“…In control experiments, 0.1% DMSO administered alone had no effect on [Ca 2ϩ ] i in the ARC neurons. Data were taken from the cells that were identified as neurons by the procedures reported previously (25,26). Briefly, the single cells that were immunoreactive for microtubule-associated protein-2, a neuron-specific marker, showed a relatively large diameter (Ն10 m) with clear and round nuclei under a phase-contrast microscope.…”

Section: Methodsmentioning

confidence: 99%

“…Correlation of [Ca 2ϩ ] i and immunocytochemical data were performed by the procedure reported previously (25)(26)(27) ] i took place within 5 min after addition of agents and their amplitudes were 150 nmol/l or larger, they were considered responses. Repetitive additions of ghrelin twice induced repeated [Ca 2ϩ ] i increases.…”

Section: Measurements Of [Camentioning

confidence: 99%

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Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus

et al. 2003

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Ghrelin is a newly discovered peptide that is released from the stomach and from neurons in the hypothalamic arcuate nucleus (ARC) and potently stimulates growth hormone release and food intake. Neuropeptide-Y (NPY) neurons in the ARC play an important role in the stimulation of food intake. The present study aimed to determine whether ghrelin directly activates NPY neurons and, if so, to explore its signaling mechanisms. Whether the neurons that respond to ghrelin could be regulated by orexin and leptin was also examined. G hrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor (GHSR), is synthesized abundantly in the stomach and to a much lesser extent in the hypothalamic arcuate nucleus (ARC) (1). Peripheral or intracerebroventricular (ICV) injection of ghrelin releases growth hormone, stimulates food intake, and increases body weight in mice, rats, and humans (1-8). ICV injection of antighrelin IgG suppresses starvation-induced feeding (3). The daily pattern of plasma ghrelin levels in normal humans is characterized by a preprandial rise and postprandial fall (9). These findings have suggested that ghrelin plays a physiological role in the meal initiation.The neuropeptide-Y (NPY)-containing neurons localized in the ARC have been implicated in the stimulation of food intake-injection of NPY into the hypothalamus of rats potently stimulates food intake (10), and NPY secretion in the hypothalamus is increased during fasting (11). Regarding a possible link between ghrelin and the NPY neurons in the ARC, it has been shown that GHSR mRNA is expressed in 94% of the NPY neurons in the ARC by double-labeling in situ hybridization histochemistry (12). Systemic or ICV administration of ghrelin causes the ARC neurons to express Fos and Egr-1 (3,13-15) and ϳ90% of these Fos-positive neurons express NPY mRNA (13). Moreover, ghrelin increases the expression of NPY mRNA (3-5), and ICV administration of a NPY Y1 antagonist suppresses the ghrelin-stimulated food intake (3-5,15). These findings suggest that the NPY neurons in the ARC could be an important effector for the orexigenic action of ghrelin.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Measurements Of [Camentioning

confidence: 99%

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Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus

et al. 2003

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Hypocretin/Orexin System

Sutcliffe

Lecea

2007

Handbook of Contemporary Neuropharmacology

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The hypocretins (also called the orexins) are excitatory neurotransmitters produced in a few thousand neurons of the lateral hypothalamus. Two G protein‐coupled receptors for the hypocretins have different distributions within the CNS and differential affinities for the two hypocretin peptides. Hypocretins efferents project to areas within the posterior hypothalamus that are implicated in feeding behaviors and hormone secretion. Hypocretin fibers also project to diverse targets in other brain regions and the spinal cord, including several areas implicated in cardiovascular function and sleep‐wake regulation. Administration of the hypocretins stimulates food intake, affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement (REM) sleep. Narcolepsy is a disorder of the hypocretin system. One aspect of hypocretin activity is the direct excitation of cholinergic forebrain neurons, brainstem monoaminergic REM‐off neurons in the locus coeruleus and dorsal raphe nucleus, and histaminergic tuberomammillary nucleus, which together suppress slow‐wave sleep. The hypocretins also modulate the activity of cholinergic REM‐on neurons in the brainstem, which gate REM entry.

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Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function

2005

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Orexin-expressing neurons in the hypothalamus project throughout the neuraxis and are involved in regulation of the sleep/wake cycle, food intake, and autonomic functions. Here we specifically analyze the anatomical organization of orexin projections to the dorsal vagal complex (DVC) and raphe pallidus and effects on ingestive behavior and autonomic functions of local orexin-A administration in nonanesthetized rats. Retrograde tracing experiments revealed that as many as 20% of hypothalamic orexin neurons project to the DVC, where they form straight varicose axon profiles, some of which are in close anatomical apposition with tyrosine hydroxylase (TH)-, glucagon-like peptide-1-, gamma-aminobutyric acid-, and nitric oxide synthase-immunoreactive neurons in a nonselective manner. Similar contacts were frequently observed with neurons of the nucleus of the solitary tract whose activation by gastrointestinal food stimuli was demonstrated by the expression of nuclear c-Fos immunoreactivity. Orexin-A administration to the fourth ventricle induced significant Fos-expression throughout the DVC compared with saline control injections, with about 20-25% of TH-ir neurons among the stimulated ones. Fourth ventricular orexin injections also significantly stimulated chow and water intake in nonfood-deprived rats. Direct bilateral injections of orexin into the DVC increased intake of palatable high-fat pellets. Orexin-ir fibers also innervated raphe pallidus. Fourth ventricular orexin-A (1 nmol) activated Fos expression in the raphe pallidus and C1/A1 catecholaminergic neurons in the ventral medulla and increased body temperature, heart rate, and locomotor activity. The results confirm that hypothalamomedullary orexin projections are involved in a variety of physiological functions, including ingestive behavior and sympathetic outflow.

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Lowering glucose concentrations increases cytosolic Ca2+ in orexin neurons of the rat lateral hypothalamus

Cited by 63 publications

References 20 publications

Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus

Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus

Hypocretin/Orexin System

Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function

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