Evans R L, Turner R J
Membrane Biology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
Eur J Morphol. 1998 Aug;36 Suppl:142-6.
In many exocrine epithelia, the Na+-K+-2Cl- cotransporter is the main provider of cellular chloride entry during transepithelial salt and water secretion. Because of its accessibility and hormonal responsiveness, the salivary gland has recently emerged as a convenient preparation in which to study the regulation and characteristics of this transport protein. In this review, we summarize recent findings from our laboratory which demonstrate that muscarinic, alpha1-adrenergic and peptidergic stimulation of rat parotid acinar cells induce a dramatic (up to twenty-fold) upregulation of Na+-K+-2Cl- cotransporter activity. Our results indicate that this effect is dependent on the rise in intracellular calcium concentration ([Ca2+]i) that accompanies stimulation, and is not a consequence of the KCl loss and the concomitant cell shrinkage associated with fluid secretion. In addition, we show that the effect of muscarinic stimulation on the cotransporter can be blocked by inhibitors of phospholipase A2, by a general inhibitor of arachidonic acid metabolism, and by specific inhibitors of the cytochrome P450 pathway. These data argue strongly for the involvement of a product of the cytochrome P450 pathway of arachidonic acid metabolism in upregulation of the salivary Na+-K+-2Cl- cotransporter.
在许多外分泌上皮中，Na⁺-K⁺-2Cl⁻协同转运蛋白是跨上皮盐和水分泌过程中细胞内氯离子进入的主要提供者。由于其易接近性和激素反应性，唾液腺最近已成为研究这种转运蛋白调节和特性的便利标本。在本综述中，我们总结了我们实验室最近的发现，这些发现表明毒蕈碱、α1-肾上腺素能和肽能刺激大鼠腮腺腺泡细胞会导致Na⁺-K⁺-2Cl⁻协同转运蛋白活性显著（高达二十倍）上调。我们的结果表明，这种效应依赖于刺激时伴随的细胞内钙浓度（[Ca²⁺]i）升高，而不是与液体分泌相关的KCl损失和随之而来的细胞收缩的结果。此外，我们表明毒蕈碱刺激对协同转运蛋白的作用可被磷脂酶A2抑制剂、花生四烯酸代谢的一般抑制剂以及细胞色素P450途径的特异性抑制剂阻断。这些数据有力地证明了花生四烯酸代谢的细胞色素P450途径的一种产物参与唾液Na⁺-K⁺-2Cl⁻协同转运蛋白的上调。
