Gobran L I, Xu Z X, Lu Z, Rooney S A
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520.
Am J Physiol. 1994 Nov;267(5 Pt 1):L625-33. doi: 10.1152/ajplung.1994.267.5.L625.
ATP is known to stimulate surfactant phospholipid secretion in type II cells, and there is evidence that this effect is mediated by a P2 purinoceptor. At least five subtypes of the P2 receptor have been reported, but it is not clear which one exists on the type II cell. To determine whether it is the P2u subtype, at which UTP is equipotent with ATP, we have compared the effects of ATP and UTP on phosphatidylcholine secretion and second messenger formation in primary cultures of rat type II cells. ATP and UTP were equally potent in stimulating phosphatidylcholine secretion and phospholipase D activation. The potency order, UTP = ATP > ADP > 2-methylthio-ATP, was the same as that reported for the P2u receptor. UTP stimulated diacylglycerol and phosphatidic acid formation to the same extent as ATP. ATP also increased choline formation. Formation of diacylglycerol was biphasic, and the first peak in response to ATP was previously shown to be associated with inositol trisphosphate formation. Northern analysis showed that the P2u receptor gene was expressed to a greater extent in type II cells than in whole lung. These data suggest that ATP and UTP act via a P2u receptor that is coupled to phosphoinositide-specific phospholipase C with subsequent activation of phospholipase D acting on phosphatidylcholine. ATP has also been reported to act at an additional type II cell receptor coupled to adenylate cyclase. In contrast, UTP did not promote adenosine 3',5'-cyclic monophosphate formation and therefore does not act at that receptor.
已知ATP可刺激II型细胞表面活性物质磷脂的分泌，且有证据表明这种作用是由P2嘌呤受体介导的。已报道P2受体至少有五种亚型，但尚不清楚II型细胞上存在的是哪一种。为了确定是否是P2u亚型（在该亚型上UTP与ATP具有同等效力），我们比较了ATP和UTP对大鼠II型细胞原代培养物中磷脂酰胆碱分泌和第二信使形成的影响。ATP和UTP在刺激磷脂酰胆碱分泌和磷脂酶D激活方面具有同等效力。效力顺序为UTP = ATP > ADP > 2-甲硫基-ATP，与报道的P2u受体相同。UTP刺激二酰基甘油和磷脂酸形成的程度与ATP相同。ATP还增加胆碱的形成。二酰基甘油的形成是双相的，先前已表明对ATP反应的第一个峰值与肌醇三磷酸的形成有关。Northern分析表明，P2u受体基因在II型细胞中的表达程度高于全肺。这些数据表明，ATP和UTP通过与磷酸肌醇特异性磷脂酶C偶联的P2u受体起作用，随后激活作用于磷脂酰胆碱的磷脂酶D。也有报道称ATP作用于与腺苷酸环化酶偶联的另一种II型细胞受体。相比之下，UTP不促进3',5'-环磷酸腺苷的形成，因此不作用于该受体。
