Orexin A and B evoke noradrenaline release from rat cerebrocortical slices

Hirota, Kazuyoshi; Kushikata, Tetsuya; Kudo, M; Kudo, Tsuyoshi; Lambert, David G.; Matsuki, Akitomo

doi:10.1038/sj.bjp.0704409

Cited by 50 publications

(39 citation statements)

References 25 publications

(39 reference statements)

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“…HCRT-immunoreactive fibers and Hcrtr 1 are present in the LC (Marcus et al, 2001). Several lines of evidence have shown that HCRT excites LC neurons (Hagan et al, 1999;Horvath et al, 1999;Soffin et al, 2002;van den Pol et al, 2002) and induces NA release from their axonal terminals in the cerebral cortex and hippocampus (Hirota et al, 2001;Walling et al, 2004). Our present data demonstrated that HCRT at high concentration (1 M) is a trigger for NA secretion from the somatodendritic region.…”

Section: Discussionsupporting

confidence: 53%

“…Our present data demonstrated that HCRT at high concentration (1 M) is a trigger for NA secretion from the somatodendritic region. These results imply that the projection from HCRT neurons to the LC may provide a pathway for HCRT modulation of LC functions, not only by regulating noradrenergic input to its targets (Hirota et al, 2001;Walling et al, 2004), but also by regulating noradrenergic transmission in its somatodendritic region. On the other hand, NMDA-type glutamate receptors are one of the major excitatory regulators of activity in LC neurons (Rasmussen, 1995).…”

Section: Discussionmentioning

confidence: 91%

“…Application of hypocretins has a direct excitatory effect on LC neurons and increases their activity (Hagan et al, 1999;Horvath et al, 1999;Soffin et al, 2002;van den Pol et al, 2002). Furthermore, hypocretins evoke noradrenaline (NA) release from the axonal terminals of LC neurons in the dentate gyrus and cerebral cortex (Hirota et al, 2001;Walling et al, 2004). Vesicles are generally released not only from axon terminals, but also from cell bodies in various cell types.…”

Section: Introductionmentioning

confidence: 99%

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Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Chen¹,

Mu²,

Huang³

et al. 2008

J. Neurosci.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Chen¹,

Mu²,

Huang³

et al. 2008

J. Neurosci.

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“…Orexins have no direct effect on VLPO neurons, but the VLPO region contains numerous orexin fibers (Chou et al 2002). We speculate that orexins act presynaptically in the VLPO region to promote release of monoamines or ACh as has been demonstrated with NE release in the cortex (Hirota et al 2001). Alternatively, orexins may enhance monoaminergic inhibition of the VLPO by reducing reuptake of monoamines.…”

Section: Integration With Current Neurophysiologymentioning

confidence: 59%

Delayed Orexin Signaling Consolidates Wakefulness and Sleep: Physiology and Modeling

Behn¹,

Brown²,

Mochizuki³

et al. 2008

Journal of Neurophysiology

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Diniz Behn CG, Kopell N, Brown EN, Mochizuki T, Scammell TE. Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling. J Neurophysiol 99: 3090 -3103, 2008. First published April 16, 2008 doi:10.1152/jn.01243.2007. Orexin-producing neurons are clearly essential for the regulation of wakefulness and sleep because loss of these cells produces narcolepsy. However, little is understood about how these neurons dynamically interact with other wake-and sleep-regulatory nuclei to control behavioral states. Using survival analysis of wake bouts in wild-type and orexin knockout mice, we found that orexins are necessary for the maintenance of long bouts of wakefulness, but orexin deficiency has little impact on wake bouts Ͻ1 min. Since orexin neurons often begin firing several seconds before the onset of waking, this suggests a surprisingly delayed onset (Ͼ1 min) of functional effects. This delay has important implications for understanding the control of wakefulness and sleep because increasing evidence suggests that different mechanisms are involved in the production of brief and sustained wake bouts. We incorporated these findings into a mathematical model of the mouse sleep/wake network. Orexins excite monoaminergic neurons and we hypothesize that orexins increase the monoaminergic inhibition of sleep-promoting neurons in the ventrolateral preoptic nucleus. We modeled orexin effects as a time-dependent increase in the strength of inhibition from wake-to sleep-promoting populations and the resulting simulated behavior accurately reflects the fragmented sleep/wake behavior of narcolepsy and leads to several predictions. By integrating neurophysiology of the sleep/wake network with emergent properties of behavioral data, this model provides a novel framework for investigating network dynamics and mechanisms associated with normal and pathologic sleep/wake behavior. I N T R O D U C T I O NOrexin-producing neurons play an essential role in the regulation of wakefulness and sleep. Loss of the orexin neurons or the orexin neuropeptides (orexin-A and -B, also known as hypocretin-1 and -2) causes narcolepsy, a common sleep disorder characterized by excessive daytime sleepiness, rapid eye movement (REM) sleep soon after sleep onset, disturbed nocturnal sleep, and cataplexy (Dauvilliers et al. 2007;Scammell 2003). Mice, rats, and dogs with disrupted orexin signaling all have sleepiness and cataplexy strikingly similar to that seen in people with narcolepsy (Beuckmann et al. 2004; Chemelli et al. 1999;Hungs and Mignot 2001).These features of narcolepsy highlight the necessity of orexins, but little is understood about how the orexin neurons dynamically interact with other wake-and sleep-regulatory nuclei to modulate sleep/wake behavior. The orexin neurons are strictly wake-active (Lee et al. 2005;Mileykovskiy et al. 2005) and send excitatory projections to many state-regulatory nuclei . Although orexin knockout (OXKO) mice have normal hourly amounts of wakefulness and sleep, their wake bouts are much s...

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“…Human variants of OX 1 and OX 2 receptors share a 64% sequence identity. Many studies suggest Ca 2ϩ influx as the most immediate cellular response to orexin receptor activation in different systems (van den Pol et al, 1998(van den Pol et al, , 1999Lund et al, 2000;Hirota et al, 2001;Kukkonen and Åkerman, 2001;Uramura et al, 2001;Holmqvist et al, 2002). This Ca 2ϩ influx may in some systems occur via protein kinase C-dependent activation of voltage-gated Ca 2ϩ channels (van den Pol et al, 1998;Uramura et al, 2001;Xu et al, 2002) but a different type of Ca 2ϩ channel has been implicated in other systems (Lund et al, 2000;Kukkonen and Åkerman, 2001).…”

mentioning

confidence: 99%

Distinct Recognition of OX₁ and OX₂Receptors by Orexin Peptides

Ammoun¹,

Holmqvist²,

Shariatmadari³

et al. 2003

J Pharmacol Exp Ther

166

119

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In this study, we have compared the abilities of orexin-A and orexin-B and variants of orexin-A to activate different Ca 2ϩ responses (influx and release) in human OX 1 and OX 2 receptorexpressing Chinese hamster ovary cells. Responses mediated by activation of both receptor subtypes with either orexin-A or -B were primarily dependent on extracellular Ca 2ϩ , suggesting similar activation of Ca 2ϩ influx as we have previously shown for orexin-A and OX 1 receptors. Amino acid-wise truncation of orexin-A reduced its ability to activate OX 1 and OX 2 receptors, but the response mediated by the OX 2 receptor was more resistant to truncation than the response mediated by the OX 1 receptor. We also performed a sequential replacement of amino acids 14 to 26 with alanine in the truncated orexin-A variant orexin-A 14 -33 . Replacement of the same amino acids produced a fall in the potency for each receptor subtype, but the reduction was less prominent for the OX 2 receptor. The most marked reduction was produced by the replacement of Leu20, Asp25, and His26 with alanine. Interestingly, extracellular Ca 2ϩ dependence of responses to some of the mutated peptides was different from those of orexin-A and -B. The mutagenesis also suggests that although the determinants required from orexin-A for binding to and activation of the receptor are highly conserved between the orexin receptor subtypes, the OX 2 receptor requires fewer determinants. This might in part explain why orexin-B has the affinity and potency equal to orexin-A for this subtype, although it has 10-to 100-fold lower affinity and potency for the OX 1 receptor.Recently, two novel hypothalamic peptides were isolated and subsequently named orexin-A and orexin-B (Sakurai et al., 1998) or hypocretin-1 and hypocretin-2 (de Lecea et al., 1998). Despite some initial confusion, orexin-A should now be considered identical to hypocretin-1 and orexin-B to hypocretin-2. Orexins act as agonists on two G-protein-coupled receptors called OX 1 and OX 2 receptors. Increased wakefulness and reduced sleep is a well demonstrated response to central administration of orexin, and disruption of central orexinergic signaling leads to the sleep disorder narcolepsy in animal models and probably also in man (reviewed in Beuckmann and Yanagisawa, 2002;Kukkonen et al., 2002;Sutcliffe and de Lecea, 2002). The other physiological roles for orexins may be regulation of energy homeostasis and stress response, probably both via central and peripheral mechanisms (reviewed in Willie et al., 2001;Beuckmann and Yanagisawa, 2002;Kirchgessner, 2002;Kukkonen et al., 2002;Smart and Jerman, 2002).The two orexin peptides, orexin-A and -B, are both products of the same precursor peptide, preproorexin, cleavage of which results in equimolar amounts of orexin-A and orexin-B. Orexin-A is composed of 33 amino acids and it contains two disulfide bridges, whereas orexin-B is a linear peptide of 28 residues (Sakurai et al., 1998). Although a product of a different part of the precursor peptide, orexin-B sho...

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Orexin A and B evoke noradrenaline release from rat cerebrocortical slices

Cited by 50 publications

References 25 publications

Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Delayed Orexin Signaling Consolidates Wakefulness and Sleep: Physiology and Modeling

Distinct Recognition of OX₁ and OX₂Receptors by Orexin Peptides

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Orexin A and B evoke noradrenaline release from rat cerebrocortical slices

Cited by 50 publications

References 25 publications

Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons

Delayed Orexin Signaling Consolidates Wakefulness and Sleep: Physiology and Modeling

Distinct Recognition of OX1 and OX2Receptors by Orexin Peptides

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Distinct Recognition of OX₁ and OX₂Receptors by Orexin Peptides