title: Orexinergic system in the locus coeruleus modulates the CO2 ventilatory response.
abstract: The orexins are hypothalamic neuropeptides involved in an array of functions such as regulation of sleep/wake states and chemoreception to CO2/pH. The locus coeruleus (LC) is a chemosensitive site and expresses an extensive population of orexin receptor 1 (OX1R). We tested the hypothesis that OX1Rs located in the LC participate in the ventilatory response to hypercapnia in a vigilance state and diurnal cycle-dependent manner. For this, we performed unilateral injections of SB-334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats and evaluated the ventilatory response to 7 % CO2 during wakefulness and sleep in the dark and light phases of the diurnal cycle. Hypercapnia induced an increase in ventilation (V E) in all groups compared to normocapnic values. However, during the dark phase, but not in the light phase, SB-334867 injection promoted an attenuation of the hypercapnic chemoreflex during wakefulness (V E: vehicle, 1502.6 ± 100 mL kg(-1) min(-1) vs SB-334867, 1200.3 ± 70.0 mL kg(-1) min(-1)) but not during sleep (V E: vehicle, 1383.0 ± 113.9 vs SB-334687, 1287.6 ± 92.1 mL kg(-1) min(-1)), due to changes in tidal volume (V T). We suggest that projections of orexin-containing neurons to the LC contribute, via OX1Rs, to the hypercapnic chemoreflex during wakefulness in the dark phase.
authors.affiliation: Department of Animal Morphology and Physiology, Sao Paulo State University-UNESP/FCAV at Jaboticabal, Jaboticabal, SP, Brazil.
authors.forename: Mariane C
authors.initials: MC
authors.lastname: Vicente
authors.affiliation: Department of Physiology, Institute of Bioscience, São Paulo State University-UNESP, Botucatu, SP, Brazil.
authors.forename: Mirela B
authors.initials: MB
authors.lastname: Dias
authors.affiliation: Department of Animal Morphology and Physiology, Sao Paulo State University-UNESP/FCAV at Jaboticabal, Jaboticabal, SP, Brazil.
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Fonseca
authors.affiliation: Department of Animal Morphology and Physiology, Sao Paulo State University-UNESP/FCAV at Jaboticabal, Jaboticabal, SP, Brazil.
authors.forename: Kênia C
authors.initials: KC
authors.lastname: Bícego
authors.affiliation: Department of Animal Morphology and Physiology, Sao Paulo State University-UNESP/FCAV at Jaboticabal, Jaboticabal, SP, Brazil. lucihel@fcav.unesp.br.
authors.forename: Luciane H
authors.initials: LH
authors.lastname: Gargaglioni
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism*; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000378:metabolism*; D012123:Pulmonary Ventilation; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex; D012890:Sleep; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014851:Wakefulness
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; C578627:Hcrtr1 protein, rat; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D002245:Carbon Dioxide; D014508:Urea
keywords: Awake; Chemoreception; Hypercapnia; Orexin; Sleep; Ventilation
references.citation: J Neurosci. 2001 Mar 1;21(5):1656-62
references.pmid: 11222656
references.citation: J Appl Physiol (1985). 2010 May;108(5):1417-24
references.pmid: 20133433
references.citation: Acta Physiol Acad Sci Hung. 1975;46(3):201-17
references.pmid: 1236228
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R47-63
references.pmid: 16959861
references.citation: Arch Ital Biol. 2001 Apr;139(3):313-28
references.pmid: 11330208
references.citation: J Neurosci. 1981 Aug;1(8):876-86
references.pmid: 7346592
references.citation: Neurology. 2014 Jan 21;82(3):271-8
references.pmid: 24363130
references.citation: Respir Physiol Neurobiol. 2014 Jan 1;190:86-95
references.pmid: 24035835
references.citation: Prog Brain Res. 2012;198:25-46
references.pmid: 22813968
references.citation: Sleep. 2004 Aug 1;27(5):851-6
references.pmid: 15453542
references.citation: Semin Neurol. 2004 Sep;24(3):211-23
references.pmid: 15449215
references.citation: Respir Physiol Neurobiol. 2010 Jan 31;170(1):96-102
references.pmid: 19995618
references.citation: J Comp Neurol. 1999 Dec 13;415(2):145-59
references.pmid: 10545156
references.citation: Brain Res. 2000 Mar 31;860(1-2):181-9
references.pmid: 10727641
references.citation: Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):176-82
references.pmid: 11295245
references.citation: Science. 1975 Jul 4;189(4196):55-8
references.pmid: 1094539
references.citation: J Physiol. 2009 May 1;587(Pt 9):2059-67
references.pmid: 19273574
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8733-8
references.pmid: 8710940
references.citation: Exp Physiol. 2014 Jan;99(1):232-47
references.pmid: 24058188
references.citation: J Appl Physiol (1985). 2007 Nov;103(5):1772-9
references.pmid: 17717124
references.citation: Brain Res. 2004 Dec 31;1030(2):165-71
references.pmid: 15571666
references.citation: J Chem Neuroanat. 2002 Jan;23(1):49-58
references.pmid: 11756009
references.citation: Brain Res. 1999 May 8;827(1-2):243-60
references.pmid: 10320718
references.citation: Cell. 1998 Feb 20;92(4):573-85
references.pmid: 9491897
references.citation: J Neurosci. 2002 Apr 1;22(7):2862-72
references.pmid: 11923451
references.citation: J Neurosci. 1998 Dec 1;18(23):9996-10015
references.pmid: 9822755
references.citation: Synapse. 2011 Sep;65(9):843-57
references.pmid: 21308795
references.citation: J Physiol. 2004 Jul 1;558(Pt 1):283-94
references.pmid: 15146040
references.citation: Am J Physiol. 1974 Aug;227(2):264-7
references.pmid: 4851837
references.citation: J Physiol. 2010 Aug 1;588(Pt 15):2935-44
references.pmid: 20547681
references.citation: Biochem Biophys Res Commun. 2002 Feb 1;290(4):1237-45
references.pmid: 11811995
references.citation: Expert Rev Mol Med. 2008 Oct 02;10:e28
references.pmid: 18828950
references.citation: Prog Neurobiol. 2008 Jul;85(3):237-72
references.pmid: 18514380
references.citation: Neuroreport. 2000 Sep 11;11(13):2991-5
references.pmid: 11006981
references.citation: Neuroscience. 2008 May 15;153(3):860-70
references.pmid: 18424001
references.citation: Neuroscience. 2001;108(2):177-81
references.pmid: 11734353
references.citation: Respir Physiol Neurobiol. 2010 Oct 31;173(3):264-73
references.pmid: 20435170
references.citation: Neuroscience. 2001;103(3):777-97
references.pmid: 11274794
references.citation: J Comp Neurol. 2001 Jun 18;435(1):6-25
references.pmid: 11370008
references.citation: J Comp Neurol. 2005 Jan 10;481(2):160-78
references.pmid: 15562511
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):322-7
references.pmid: 9419374
references.citation: Respir Physiol. 1970 Oct;10 (3):384-95
references.pmid: 5476156
references.citation: J Appl Physiol (1985). 2005 Apr;98(4):1387-95
references.pmid: 15557013
references.citation: Respir Physiol Neurobiol. 2010 Jun 30;172(1-2):24-31
references.pmid: 20416403
references.citation: Respir Physiol Neurobiol. 2013 Jan 15;185(2):349-55
references.pmid: 22999917
references.citation: Pflugers Arch. 2010 Feb;459(3):357-68
references.pmid: 19844739
references.citation: Sleep Med. 2005 Jun;6 Suppl 1:S3-7
references.pmid: 16140243
references.citation: Acta Physiol (Oxf). 2013 May;208(1):125-35
references.pmid: 23414221
references.citation: Neuron. 2005 Jun 2;46(5):787-98
references.pmid: 15924864
references.citation: J Physiol. 2002 May 15;541(Pt 1):169-85
references.pmid: 12015428
references.citation: J Neurosci. 2005 Jul 13;25(28):6716-20
references.pmid: 16014733
references.citation: J Appl Physiol (1985). 2002 May;92(5):2119-30
references.pmid: 11960965
references.citation: Neuropharmacology. 2002 Jan;42(1):127-33
references.pmid: 11750922
references.citation: J Neurosci. 2000 Oct 15;20(20):7760-5
references.pmid: 11027239
references.citation: Auton Neurosci. 2011 Apr 26;161(1-2):20-7
references.pmid: 20813590
references.citation: J Physiol. 1996 Feb 15;491 ( Pt 1):261-9
references.pmid: 9011618
references.citation: Front Neuroendocrinol. 2008 Jan;29(1):70-87
references.pmid: 17910982
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1981 Jul;51(1):78-83
references.pmid: 6790501
references.citation: Nat Med. 2007 Feb;13(2):150-5
references.pmid: 17259994
references.citation: FEBS Lett. 1998 Oct 30;438(1-2):71-5
references.pmid: 9821961
references.citation: Behav Brain Funct. 2007 Jun 13;3:28
references.pmid: 17567902
references.citation: Indian J Med Res. 2007 Jun;125(6):721-39
references.pmid: 17704548
references.citation: Pflugers Arch. 2008 Mar;455(6):1119-28
references.pmid: 17851683
references.citation: J Appl Physiol (1985). 2007 Jan;102(1):241-8
references.pmid: 16959906
references.citation: Pflugers Arch. 1987 Jun;409(1-2):1-6
references.pmid: 3112732
references.citation: Curr Opin Pulm Med. 2008 Nov;14(6):512-8
references.pmid: 18812827
references.citation: Brain Res. 2001 May 18;901(1-2):259-64
references.pmid: 11368975