title: Endogenous acetylcholine increases alveolar epithelial fluid transport via activation of alveolar epithelial Na,K-ATPase in mice.
abstract: The contribution of endogenous acetylcholine to alveolar fluid clearance (AFC) and related molecular mechanisms were explored. AFC was measured in Balb/c mice after vagotomy and vagus nerve stimulation. Effects of acetylcholine chloride on AFC in Kunming mice and Na,K-ATPase function in A549 alveolar epithelial cells also were determined. AFC significantly decreased in mice with left cervical vagus nerve transection compared with controls (48.69 ± 2.57 vs. 66.88 ± 2.64, P ≤ 0.01), which was reversed by stimulation of the peripheral (60.81 ± 1.96, P ≤ 0.01). Compared with control, acetylcholine chloride dose-dependently increased AFC and elevated Na,K-ATPase activity, and these increases were blocked or reversed by atropine. These effects were accompanied by recruitment of Na,K-ATPase α1 to the cell membrane. Thus, vagus nerves participate in alveolar epithelial fluid transport by releasing endogenous acetylcholine in the infusion-induced pulmonary edema mouse model. Effects of endogenous acetylcholine on AFC are likely mediated by Na,K-ATPase function through activation of muscarinic acetylcholine receptors on alveolar epithelia.
authors.affiliation: The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China. Electronic address: lix0518@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Pulmonary of Second Affiliated Hospital, Hebei Medical University, Shijiazhuang 050000, China. Electronic address: xi_xin_yan@163.com.
authors.forename: Xi Xin
authors.initials: XX
authors.lastname: Yan
authors.affiliation: Division of Pulmonary of Second Affiliated Hospital, Hebei Medical University, Shijiazhuang 050000, China. Electronic address: lihl05@sina.com.
authors.forename: Hong Lin
authors.initials: HL
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China. Electronic address: lrq640225@163.com.
authors.forename: Rong Qin
authors.initials: RQ
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D045744:Cell Line, Tumor; D015633:Extravascular Lung Water / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011654:Pulmonary Edema / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D055536:Vagus Nerve Stimulation
chemical_list: D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D001285:Atropine; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine
keywords: Alveolar fluid clearance; Endogenous acetylcholine; Na,K-ATPase; Vagus nerve stimulation