Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5

Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5
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DOI:
10.1006/exer.1999.0814
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发表时间:
2000-05-01
影响因子:
3.4
通讯作者:
Verkman, AS
Verkman, AS
中科院分区:
医学3区
文献类型:
--
作者:
Moore, M;Ma, TH;Verkman, AS

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已有报道三种水通道蛋白(AQP)型水通道在泪腺中表达:AQP 5在腺泡和导管细胞的顶膜中,AQP 4在腺泡细胞的基底外侧膜中,AQP 1在微血管内皮中。最近的实验表明,水运动通过AQP 5在唾液腺是重要的唾液分泌。为了研究水通道蛋白在泪腺功能中的作用,在野生型小鼠和缺乏AQP 1、AQP 4和AQP 5以及AQP 3的基因敲除小鼠中比较了基础和毛果芸香碱刺激的泪液分泌,AQP 3在腺泡细胞的基底外侧膜中表达。在毛果芸香碱给药前和给药后4 min,使用微毛细管收集麻醉小鼠的泪液。泪液体积为(μ l/4 min,S.E.):0.69+/- 0.06(野生型小鼠)、0.70 +/- 0.07(AQP 1-/-)、0.81 +/- 0.13(AQP 3-/-)、0.62 +/- 0.14(AQP 4-/-)和0.78 +/- 0.09(AQP 5-/-)(差异不显著)。通过荧光测定法测量的氯化物浓度(平均155 +/- 13 mM)在从野生型与水通道蛋白缺失小鼠收集的泪液中也没有差异。这些发现为水通道蛋白在泪腺液体分泌中的重要作用提供了直接证据。唾液而不是泪腺分泌中对水通道蛋白的需求可能涉及泪腺大腺泡细胞的液体分泌速率显著减慢。(C)北京大学出版社.
The expression of three aquaporin (AQP)-type water channels has been reported in the lacrimal gland: AQP5 in the apical membranes of acinar and duct cells, AQP4 in the basolateral membranes of acinar cells, and AQP1 in microvascular endothelia. Recent experiments indicate that water movement through AQP5 in the salivary grand is important in saliva secretion. To investigate the role of aquaporins in lacrimal gland function, basal and pilocarpine-stimulated tear secretion was compared in wildtype mice and knockout mice lacking AQP1, AQP4 and AQP5, as well as AQP3, which was found here to be expressed in the basolateral membrane of acinar cells. Tear fluid was collected in anesthetized mice using microcapillary tubes before and at 4 min intervals after pilocarpine administration. Tear fluid volumes were (in mu l per 4 min, S.E.): 0.69 +/- 0.06 (wildtype mice), 0.70 +/- 0.07 (AQP1 -/-), 0.81 +/- 0.13 (AQP3 -/-), 0.62 +/- 0.14 (AQP4 -/-), and 0.78 +/- 0.09 (AQP5 -/-) (differences not significant). Chloride concentrations (average 155 +/- 13 mM) measured by a fluorescence assay were also not different in tear fluid collected from wildtype vs aquaporin null mice. These findings provide direct evidence against an essential role for aquaporins in lacrimal gland fluid secretion, The requirement for aquaporins in salivary but not lacrimal gland secretion, may involve the substantially slower fluid secretion rate across lacrimal grand acinar cells. (C) 2000 Academic Press.