ナガサカ　ヤスコ   NAGASAKA Yasuko   長坂　安子    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Sensitivity to Sevoflurane anesthesia is decreased in mice with a congenital deletion of Guanylyl Cyclase-1 alpha.
掲載誌名	正式名：BMC anesthesiology 略　 称：BMC Anesthesiol ISSNコード：14712253/14712253
掲載区分	国外
巻・号・頁	17(1),pp.76
国際共著	国際共著
著者・共著者	Nagasaka Yasuko, Wepler Martin, Thoonen Robrecht, Sips Patrick Y, Allen Kaitlin, Graw Jan A, Yao Vincent, Burns Sara M, Muenster Stefan, Brouckaert Peter, Miller Keith, Solt Ken, Buys Emmanuel S, Ichinose Fumito, Zapol Warren M
発行年月	2017/06
概要	BACKGROUND:Volatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness.METHODS:Sevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1-/- mice). Spatial distributions of GC-1α and the GC-2α subunit in the brain were visualized by in situ hybridization. Brain cGMP levels were measured in WT and GC-1-/- mice after inhaling oxygen with or without 1.2% sevoflurane for 20 min.RESULTS:Higher concentrations of sevoflurane were required to induce LORR in GC-1-/- mice than in WT mice (1.5 ± 0.1 vs. 1.1 ± 0.2%, respectively, n = 14 and 14, P < 0.0001). Similarly, RORR occurred at higher concentrations of sevoflurane in GC-1-/- mice than in WT mice (1.0 ± 0.1 vs. 0.8 ± 0.1%, respectively, n = 14 and 14, P < 0.0001). Abundant GC-1α and GC-2α mRNA expression was detected in the cerebral cortex, medial habenula, hippocampus, and cerebellum. Inhaling 1.2% sevoflurane for 20 min increased cGMP levels in the brains of WT mice from 2.6 ± 2.0 to 5.5 ± 3.7 pmol/mg protein (n = 13 and 10, respectively, P = 0.0355) but not in GC-1-/- mice.CONCLUSION:Congenital deficiency of GC-1α abolished the ability of sevoflurane anesthesia to increase cGMP levels in the whole brain, and increased the concentration of sevoflurane required to induce LORR. Impaired NO-cGMP signaling raises the threshold for producing sevoflurane-induced unconsciousness in mice.
DOI	10.1186/s12871-017-0368-5
PMID	28615047