title: Dynamic analysis of histamine-mediated attenuation of acetylcholine-induced sweating via GSK3β activation.
abstract: Sweating has been associated with the exacerbation of atopic dermatitis (AD) in diverse ways. Acetylcholine (ACh)-mediated sweating is known to be attenuated in AD, but its cause remains obscure. To address this issue, the impact of histamine on ACh-induced sweating was evaluated. Sweating was measured by counting the number of active sweat pores by the starch-iodine reaction and dynamic optical coherence tomography; sweat was visualized using two-photon excitation fluorescence microscopy in mice and the quantitative sudomotor axon reflex test in humans. Both histamine receptor antagonists and H1 receptor (H1R)-knockout (KO) mice were used to determine methodological specificity. Histamine demonstrably inhibited ACh-induced sweating in both mice and humans via H1R-mediated signaling. In sweat glands, ACh inactivated glycogen synthase kinase 3β (GSK3β), a kinase involved in endocytosis and secretion, whereas simultaneous stimulation with histamine activated GSK3β. Results of two-photon excitation fluorescence microscopy confirmed the dynamic motion of sweat and sweat glands after ACh treatment, showing that simultaneous stimulation with histamine altered their dynamic properties. These results indicate that histamine inhibits sweat gland secretions by blocking ACh-induced inactivation of GSK3β. Histamine-mediated hypohidrosis might be involved in the mechanism of abnormal skin dryness in patients with AD.
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: h-murota@derma.med.osaka-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Physiology, College of Medicine, Soonchunhyang University, Chenan, Republic of Korea.
authors.forename: Jeong-Beom
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Course of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Kouta
authors.initials: K
authors.lastname: Omiya
authors.affiliation: Course of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ohmi
authors.affiliation: Laboratory of Cellular Dynamics, WPI-Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.affiliation: Laboratory of Cellular Dynamics, WPI-Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D060833:Cellular Microenvironment / Q000502:physiology; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D064368:Healthy Volunteers; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007007:Hypohidrosis / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011969:Receptors, Histamine H1 / Q000235:genetics*; D012018:Reflex / Q000502:physiology; D013545:Sweat Glands / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D013546:Sweating / Q000187:drug effects / Q000502:physiology*
chemical_list: D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D006632:Histamine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D000109:Acetylcholine
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