REGULATION OF TRANSPORT ACROSS PULMONARY ALVEOLAR EPITHELIAL-CELL MONOLAYERS

REGULATION OF TRANSPORT ACROSS PULMONARY ALVEOLAR EPITHELIAL-CELL MONOLAYERS
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DOI:
10.1152/jappl.1984.57.3.703
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发表时间:
1984-01-01
影响因子:
3.3
通讯作者:
CRANDALL, ED
CRANDALL, ED
中科院分区:
医学2区
文献类型:
--
作者:
GOODMAN, BE;BROWN, SES;CRANDALL, ED

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原代培养的大鼠肺II型肺泡上皮细胞单层大量形成圆顶。这些充满流体的结构是由溶质从介质向下层主动输送而形成的,水被动地跟随。通过测定cAMP类似物、磷酸二酯酶抑制剂、神经递质和加压素(抗利尿激素,ADH)对圆顶形成的影响,使用圆顶形成单层来研究肺泡上皮运输过程的调节。cAMP类似物(二丁酰cAMP和8-溴-cAMP)和磷酸二酯酶抑制剂(茶碱、罂粟碱和异丁基甲基黄嘌呤)在24小时内引起圆顶形成的大幅增加。ADH和β-肾上腺素能激动剂(肾上腺素、特布他林和异丙肾上腺素)也引起圆顶密度的显著增加。β-激动剂反应在β-阻滞剂普萘洛尔。二丁酰鸟苷3“,5”-环一磷酸和乙酰胆碱(胆碱能激动剂)对圆顶形成没有影响,而α-鸟苷3“,5”-环一磷酸和乙酰胆碱(胆碱能激动剂)对圆顶形成没有影响。肾上腺素能激动剂甲氧胺引起圆顶形成的小但显著的减少。这些研究结果表明,活性溶质通量导致圆顶形成II型肺泡上皮细胞单层增加的物质,预计提高细胞内cAMP(或类似物)浓度。一个有吸引力的推测,肺液体平衡的主要影响是,transepithelial流量可以调节内源性,也许是外源性的,在成年哺乳动物肺泡上皮细胞在体内的化学试剂。
Domes are formed in large numbers by primary cultured monolayers of type II alveolar epithelial cells from rat lungs. These fluid-filled structures are formed by active transport of solute from medium to substratum, with water following passively. Dome-forming monolayers were used to study the regulation of alveolar epithelial transport processes by determining the effects on dome formation of cAMP analogs, phosphodiesterase inhibitors, neurotransmitters and vasopressin (antidiuretic hormone, ADH). The cAMP analogs (dibutyryl cAMP and 8-bromo-cAMP) and phosphodiesterase inhibitors (theophylline, papaverine and isobutylmethylxanthine) caused large increases in dome formation by 24 h. ADH and .beta.-adrenergic agonists (epinephrine, terbutaline and isoproterenol) also caused significant increases in dome density. The .beta.-agonist response was completely eliminated in the presence of the .beta.-blocker propranolol. Dibutyryl guanosine 3'',5''-cyclic monophosphate and acetylcholine (cholinergic agonist) had no effect on dome formation, whereas the .alpha.-adrenergic agonist methoxamine caused a small but significant decrease in dome formation. These findings suggest that the active solute flux resulting in dome formation by type II alveolar epithelial cell monolayers is increased by substances expected to elevate intracellular cAMP (or analogue) concentrations. An attractive speculation having major implications for lung fluid balance is that transepithelial fluxes can be modulated by endogenous, and perhaps exogenous, chemical agents in adult mammalian alveolar epithelium in vivo.