Adir Yochai, Azzam Zaher S, Lecuona Emilia, Leal Sergio, Pesce Liuska, Dumasius Vidas, Bertorello Alejandro M, Factor Phillip, Young James B, Ridge Karen M, Sznajder Jacob Iasha
Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611-3010, USA.
Am J Respir Crit Care Med. 2004 Mar 15;169(6):757-63. doi: 10.1164/rccm.200207-744OC. Epub 2003 Dec 30.
We have previously reported that dopamine increased active Na+ transport in rat lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether alveolar epithelial cells produce dopamine and whether increasing endogenous dopamine production by feeding rats a 4% tyrosine diet (TSD) would increase lung liquid clearance. Alveolar Type II cells express the enzyme aromatic-L-amino acid decarboxylase (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L-tyrosine (L-dopa), produce dopamine. Rats fed TSD, a precursor of L-dopa and dopamine, had increased urinary dopamine levels, which were inhibited by benserazide, an inhibitor of AADC. Rats fed TSD for 15, 24, and 48 hours had a 26, 46, and 45% increase in lung liquid clearance, respectively, as compared with controls. Also, dopaminergic D1 receptor antagonist--but not dopaminergic D2 receptor antagonist--inhibited the TSD-mediated increase in lung liquid clearance. Alveolar Type II cells isolated from the lungs of rats after they had been fed TSD for 24 hours demonstrated increased protein abundance of Na,K-ATPase alpha1 and beta1 subunits. Basolateral membranes isolated from peripheral lung tissue of tyrosine-fed rats had increased Na,K-ATPase activity and Na,K-ATPase alpha1 subunit. These data provide the first evidence that alveolar epithelial cells produce dopamine and that increasing endogenous dopamine increases lung liquid clearance.
我们之前曾报道，多巴胺通过上调肺泡上皮钠钾ATP酶来增加大鼠肺中的主动钠转运。在此，我们测试了肺泡上皮细胞是否产生多巴胺，以及给大鼠喂食4%酪氨酸饮食（TSD）以增加内源性多巴胺生成是否会提高肺液清除率。II型肺泡细胞表达芳香族L-氨基酸脱羧酶（AADC），并且在与多巴胺前体3-羟基-L-酪氨酸（L-多巴）一起孵育时会产生多巴胺。喂食TSD（L-多巴和多巴胺的前体）的大鼠尿多巴胺水平升高，这被AADC抑制剂苄丝肼所抑制。与对照组相比，喂食TSD 15、24和48小时的大鼠肺液清除率分别提高了26%、46%和45%。此外，多巴胺能D1受体拮抗剂——而非多巴胺能D2受体拮抗剂——抑制了TSD介导的肺液清除率增加。从喂食TSD 24小时的大鼠肺中分离出的II型肺泡细胞显示钠钾ATP酶α1和β1亚基的蛋白丰度增加。从喂食酪氨酸的大鼠外周肺组织分离出的基底外侧膜具有增加的钠钾ATP酶活性和钠钾ATP酶α1亚基。这些数据首次证明肺泡上皮细胞产生多巴胺，并且内源性多巴胺增加会提高肺液清除率。
