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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-10-29
pubmed:abstractText
We have previously shown that hypercapnic chemoreflex in prepro-orexin knockout mice (ORX-KO) is attenuated during wake but not sleep periods. In that study, however, hypercapnic stimulation had been chronically applied for 6 h because of technical difficulty in changing the composition of the inspired gas mixture without distorting the animal's vigilance states. In the present study we examined possible involvement of orexin in acute respiratory chemoreflex during wake periods. Ventilation was recorded together with electroencephalography and electromyography before and after intracerebroventricular administration of orexin or an orexin receptor antagonist, SB-334867. A hypercapnic (5 or 10% CO(2)) or hypoxic (15 or 10% O(2)) gas mixture was introduced into the recording chamber for 5 min. Respiratory parameters were analyzed only for quiet wakefulness. When mice breathed normal room air, orexin-A and orexin-B but not vehicle or SB-334867 increased minute ventilation in both ORX-KO and wild-type (WT) mice. As expected, hypercapnic chemoreflex in vehicle-treated ORX- KO mice (0.22 +/- 0.03 mlxmin(-1)xg(-1)x% CO(2)(-1)) was significantly blunted compared with that in WT mice (0.51 +/- 0.05 mlxmin(-1)xg(-1)x% CO(2)(-1)). Supplementation of orexin-A or -B (3 nmol) partially restored the hypercapnic chemoreflex in ORX-KO mice (0.28 +/- 0.03 mlxmin(-1).g(-1)x% CO(2)(-1) for orexin-A and 0.32 +/- 0.04 mlxmin(-1)xg(-1)x% CO(2)(-1) for orexin-B). In addition, injection of SB-334867 (30 nmol) in WT mice decreased the hypercapnic chemoreflex (0.39 +/- 0.04 mlxmin(-1)xg(-1)x% CO(2)(-1)). On the other hand, hypoxic chemoreflex in vehicle-treated ORX-KO and SB-334867-treated WT mice was not different from that in corresponding controls. Our findings suggest that orexin plays a crucial role in CO(2) sensitivity at least during wake periods in mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
8750-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1772-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17717124-Animals, pubmed-meshheading:17717124-Anoxia, pubmed-meshheading:17717124-Benzoxazoles, pubmed-meshheading:17717124-Carbon Dioxide, pubmed-meshheading:17717124-Chemoreceptor Cells, pubmed-meshheading:17717124-Disease Models, Animal, pubmed-meshheading:17717124-Electroencephalography, pubmed-meshheading:17717124-Electromyography, pubmed-meshheading:17717124-Hypercapnia, pubmed-meshheading:17717124-Hypothalamus, pubmed-meshheading:17717124-Injections, Intraventricular, pubmed-meshheading:17717124-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17717124-Mice, pubmed-meshheading:17717124-Mice, Inbred C57BL, pubmed-meshheading:17717124-Mice, Knockout, pubmed-meshheading:17717124-Motor Activity, pubmed-meshheading:17717124-Neuropeptides, pubmed-meshheading:17717124-Pulmonary Ventilation, pubmed-meshheading:17717124-Receptors, G-Protein-Coupled, pubmed-meshheading:17717124-Receptors, Neuropeptide, pubmed-meshheading:17717124-Reflex, pubmed-meshheading:17717124-Time Factors, pubmed-meshheading:17717124-Urea, pubmed-meshheading:17717124-Wakefulness
pubmed:year
2007
pubmed:articleTitle
Contribution of orexin in hypercapnic chemoreflex: evidence from genetic and pharmacological disruption and supplementation studies in mice.
pubmed:affiliation
Dept. of Molecular & Integrative Physiology, Chiba Univ. Graduate School of Medicine, 1-8-1 Chuo-ku, Chiba 260-8670, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't