Paradiso A M, Mason S J, Lazarowski E R, Boucher R C
Department of Medicine, University of North Carolina, Chapel Hill 27599, USA.
Nature. 1995 Oct 19;377(6550):643-6. doi: 10.1038/377643a0.
Epithelial cells exist in a complex setting in which responses to mucosal or serosal environments are mediated by receptors expressed on specialized cellular domains, such as apical versus basolateral cell membranes. We investigated whether airway epithelia can react selectively through G-protein-coupled receptors to stimuli in the mucosal or serosal environments by measuring inositol phosphate and intracellular Ca2+ responses in polarized human nasal epithelial monolayers. We report here that unilateral ATP (10(-4) M) administration stimulated P2 purinoceptors and tapped pools of intracellular Ca2+ associated with the plasma membrane ipsilateral but not contralateral to stimulated receptors. Similarly, activation of plasma membrane Ca2+ influx by ATP was confined to the membrane ipsilateral to receptor stimulation. These findings demonstrate that polarized epithelia restrict P2 receptor-mediated responses to a single domain of the cell, reflecting membrane-specific generation and catabolism of inositol phosphates and confinement of calcium influx regulation to the membrane ipsilateral to the stimulated receptors.
上皮细胞存在于一个复杂的环境中,其中对黏膜或浆膜环境的反应是由特化细胞结构域(如顶端与基底外侧细胞膜)上表达的受体介导的。我们通过测量极化的人鼻上皮单层中的肌醇磷酸和细胞内Ca2+反应,研究气道上皮是否能通过G蛋白偶联受体对黏膜或浆膜环境中的刺激产生选择性反应。我们在此报告,单侧给予ATP(10(-4) M)可刺激P2嘌呤受体,并利用与受刺激受体同侧而非对侧质膜相关的细胞内Ca2+池。同样,ATP对质膜Ca2+内流的激活局限于受体刺激同侧的膜。这些发现表明,极化上皮将P2受体介导的反应限制在细胞的单个结构域,反映了肌醇磷酸的膜特异性生成和分解代谢以及钙内流调节局限于受刺激受体同侧的膜。