Division of Nephrology, Hypertension and Transplantation, Univ. of Florida College of Medicine, PO Box 100224, Gainesville, FL 32610, USA.
Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F701-13. doi: 10.1152/ajprenal.00030.2013. Epub 2013 Jun 26.
Renal glutamine synthetase catalyzes the reaction of NH4+ with glutamate, forming glutamine and decreasing the ammonia available for net acid excretion. The purpose of the present study was to determine glutamine synthetase's specific cellular expression in the mouse kidney and its regulation by hypokalemia, a common cause of altered renal ammonia metabolism. Glutamine synthetase mRNA and protein were present in the renal cortex and in both the outer and inner stripes of the outer medulla. Immunohistochemistry showed glutamine synthetase expression throughout the entire proximal tubule and in nonproximal tubule cells. Double immunolabel with cell-specific markers demonstrated glutamine synthetase expression in type A intercalated cells, non-A, non-B intercalated cells, and distal convoluted tubule cells, but not in principal cells, type B intercalated cells, or connecting segment cells. Hypokalemia induced by feeding a nominally K+ -free diet for 12 days decreased glutamine synthetase expression throughout the entire proximal tubule and in the distal convoluted tubule and simultaneously increased glutamine synthetase expression in type A intercalated cells in both the cortical and outer medullary collecting duct. We conclude that glutamine synthetase is widely and specifically expressed in renal epithelial cells and that the regulation of expression differs in specific cell populations. Glutamine synthetase is likely to mediate an important role in renal ammonia metabolism.
肾脏谷氨酰胺合成酶催化 NH4+与谷氨酸的反应，形成谷氨酰胺，减少可用于净酸排泄的氨。本研究的目的是确定谷氨酰胺合成酶在小鼠肾脏中的特定细胞表达及其对低钾血症的调节作用，低钾血症是改变肾脏氨代谢的常见原因。谷氨酰胺合成酶 mRNA 和蛋白存在于肾脏皮质和外髓质的外带和内带中。免疫组织化学显示谷氨酰胺合成酶在整个近端小管和非近端小管细胞中表达。与细胞特异性标志物的双重免疫标记显示，谷氨酰胺合成酶在外带型闰细胞、非 A 型非 B 型闰细胞和远端卷曲管细胞中表达，但在主细胞、B 型闰细胞或连接段细胞中不表达。通过喂养名义上不含 K+的饮食 12 天引起的低钾血症导致整个近端小管和远端卷曲管中的谷氨酰胺合成酶表达减少，同时在外带皮质和髓质集合管中的 A 型闰细胞中增加谷氨酰胺合成酶表达。我们得出结论，谷氨酰胺合成酶在肾脏上皮细胞中广泛且特异性表达，其表达的调节在特定细胞群体中存在差异。谷氨酰胺合成酶可能在肾脏氨代谢中发挥重要作用。
