Kim K C, Zheng Q X, Van-Seuningen I
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore, MD 21201.
Am J Respir Cell Mol Biol. 1993 Feb;8(2):121-5. doi: 10.1165/ajrcmb/8.2.121.
Release of mucins from cultured airway surface epithelial cells can be stimulated by extracellular ATP via a P2-purinergic receptor-mediated mechanism (K. C. Kim and B. C. Lee. 1991. Br. J. Pharmacol. 103:1053-1056). In this report, we studied the mechanism by which extracellular ATP induces the mucin release. We found that: (1) ATP increased both mucin release and generation of inositol phosphates in a dose-dependent fashion, and their dose-effect relationships were almost superimposed; (2) the increases in both mucin release and the phosphatidylinositol phosphate (PI) turnover by extracellular ATP were partially, but almost equally, blocked by the pretreatment with pertussis toxin (42% for mucin release and 44% for PI turnover). We conclude that in cultured airway goblet cells extracellular ATP stimulates mucin release by a signal transduction mechanism, which seems to involve coupling of ATP-activated P2 purinoceptors with phospholipase C, at least in part, via pertussis toxin-sensitive GTP-binding proteins. This may be an important finding in understanding the regulation of mucin release by airway goblet cells, since a number of agents present in the airway could influence this signal transduction pathway and subsequently modulate the mucin secretion.
细胞外ATP可通过P2-嘌呤能受体介导的机制刺激培养的气道表面上皮细胞释放黏蛋白（K.C. Kim和B.C. Lee，1991年，《英国药理学杂志》103:1053 - 1056）。在本报告中，我们研究了细胞外ATP诱导黏蛋白释放的机制。我们发现：（1）ATP以剂量依赖的方式增加黏蛋白释放和肌醇磷酸的生成，且它们的剂量效应关系几乎重叠；（2）细胞外ATP引起的黏蛋白释放增加和磷脂酰肌醇磷酸（PI）周转增加，部分但几乎同等程度地被百日咳毒素预处理所阻断（黏蛋白释放阻断42%，PI周转阻断44%）。我们得出结论，在培养的气道杯状细胞中，细胞外ATP通过一种信号转导机制刺激黏蛋白释放，该机制似乎至少部分地通过百日咳毒素敏感的GTP结合蛋白，涉及ATP激活的P2嘌呤受体与磷脂酶C的偶联。这可能是理解气道杯状细胞黏蛋白释放调节的一个重要发现，因为气道中存在的许多物质可能影响这一信号转导途径，进而调节黏蛋白分泌。
