Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia
Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia
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DOI：
10.1113/jphysiol.2008.167395
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发表时间：
2009-06-15
影响因子：
5.5
通讯作者：
Arreola, Jorge
中科院分区：
文献类型：
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作者：
Casas-Pruneda, Griselda;Pablo Reyes, Juan;Arreola, Jorge
小鼠腮腺腺泡细胞表达P2X(4)和P2X(7)受体(mP2X(4)R和mP2X(7)R)，其生理功能尚未确定。在这里，我们发现在HEK-293细胞中表达的mP2X(4)R不允许四乙基铵（TEA(+)）通过，并且当受到ATP或BzATP刺激时，几乎不促进溴化乙酯（EtBr）的摄取。相比之下，mP2X(7)R产生缓慢衰减的TEA（+）电流，持续的Na+电流，并促进稳健的EtBr摄取。然而，来自腺泡细胞的atp激活的TEA（+）电流与mP2X(7)R或mP2X(4)R产生的电流不同。在不同mP2X(4): mP2X(7) cDNA比例共转染HEK细胞并使用含有TEA（+）或Na+离子的溶液中，研究了mP2X(4)R和mP2X(7)R之间的功能相互作用。在ATP刺激下，共表达通道产生TEA（+）电流，其衰减速度比单独使用mP2X(7)R更快。此外，转染2:1 cDNA比例的细胞表现出与在腺泡细胞中观察到的相似的衰变动力学。构建了mP2X(4)R、mP2X(7)R、mP2X(4)R: mP2X(7)R共表达以及腺泡细胞在含Na+溶液中的浓度-响应曲线。测定的EC50值分别为11、220、434和442 μ M。表达mP2X(4)R或单独表达mP2X(7)R产生的Na+电流被伊维菌素（IVM）增强。相比之下，只有当ATP浓度从5 mM降低到0.03 mM时，共表达P2X(4)和P2X(7)（1:1或2:1 cDNA比例）的腺泡细胞和HEK细胞中的IVM增强才会出现。综上所述，我们的观察表明小鼠P2X(7)和P2X(4)受体之间存在功能相互作用。这种相互作用可能发生在腺泡细胞中，形成对唾液上皮细胞外ATP的反应。
Mouse parotid acinar cells express P2X(4) and P2X(7) receptors (mP2X(4)R and mP2X(7)R) whose physiological function remains undetermined. Here we show that mP2X(4)R expressed in HEK-293 cells do not allow the passage of tetraethylammonium (TEA(+)) and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with ATP or BzATP. In contrast, mP2X(7)R generates slowly decaying TEA(+) current, sustained Na+ current and promotes robust EtBr uptake. However, ATP-activated TEA(+) current from acinar cells was unlike that generated by mP2X(7)R or mP2X(4)R. Functional interactions between mP2X(4)R and mP2X(7)R were investigated in HEK cells co-transfected with different mP2X(4) : mP2X(7) cDNA ratios and using solutions containing either TEA(+) or Na+ ions. Co-expressed channels generated a TEA(+) current that displayed faster decay during ATP stimulation than mP2X(7)R alone. Moreover, cells transfected with a 2 : 1 cDNA ratio displayed decaying kinetics similar to those observed in acinar cells. Concentration-response curves in Na+-containing solutions were constructed for heterologously expressed mP2X(4)R, mP2X(7)R and mP2X(4)R: mP2X(7)R co-expressions as well as acinar cells. The EC50 values determined were 11, 220, 434 and 442 mu M, respectively. Na+ currents generated by expressing mP2X(4)R or mP2X(7)R alone were potentiated by ivermectin (IVM). In contrast, IVM potentiation in acinar cells and HEK cells co-expressing P2X(4) and P2X(7) (1 : 1 or 2 : 1 cDNA ratios) was seen only when the ATP concentration was lowered from 5 to 0.03 mM. Taken together our observations indicate a functional interaction between murine P2X(7) and P2X(4) receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia.