Centre of Molecular Biology and Neuroscience, Dept. of Anatomy, Institute of Basic Medical Sciences, Univ. of Oslo, Oslo, Norway.
Am J Physiol Renal Physiol. 2012 Feb 1;302(3):F316-28. doi: 10.1152/ajprenal.00464.2011. Epub 2011 Nov 9.
The Na(+)- and Cl(-)-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium-myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver.
钠（+）和氯（-）依赖性 GABA-甜菜碱转运蛋白（BGT1）主要作为肾脏中对抗渗透压变化的保护者以及大脑中神经递质 GABA 的潜在控制器而受到关注。然而，BGT1 的细胞分布及其生理重要性尚未完全了解。在这里，我们使用 TaqMan 实时 PCR 定量了 mRNA 水平，产生了一些 BGT1 抗体，并使用这些抗体研究了 BGT1 在小鼠中的分布。BGT1（蛋白和 mRNA）主要在肝脏（窦状肝细胞质膜）中表达，而不在内皮细胞中表达。BGT1 也存在于肾脏髓质中，位于集合管的基底外侧膜（特别是在乳头尖端）和亨利氏升支粗段。脑膜中有一些 BGT1，但脑实质、脑血管、室管膜细胞、肾脏皮质和肠道在 1 至 3 个月大的小鼠中几乎没有 BGT1。通过平行处理 BGT1 缺陷型同窝仔鼠作为阴性对照来确保标记特异性。将 2.5%氯化钠添加到饮用水中 48 小时会导致肾脏髓质中 BGT1、张力反应增强子结合蛋白和钠-肌醇共转运蛋白 1（slc5a3）的两倍至三倍上调，但在大脑中没有上调，在肝脏中几乎没有上调。BGT1 缺陷型和野生型小鼠似乎对盐处理的耐受性相同，可能是因为甜菜碱是几种渗透物之一。总之，这项研究表明，BGT1 主要在肝脏中发挥作用，从而补充了其他主要在小肠或肾脏而不是肝脏中表达的甜菜碱转运载体蛋白（例如 slc6a20）。
