Department of Oral & Maxillofacial Surgery and Systemic Medicine, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan.
Acta Odontol Scand. 2013 Mar;71(2):312-6. doi: 10.3109/00016357.2012.680904. Epub 2012 May 8.
Various substances including uric acid, organic acids and drugs are transported by organic anion transporters (OATs) in the kidney. In addition, a member of the OAT family, urate transporter 1 (URAT1), is involved in the reabsorption of uric acid from the renal tubule. Benzbromarone inhibits URAT1 to block uric acid reabsorption.
Our group previously observed higher salivary uric acid levels than serum levels in patients taking benzbromarone, and reported the possible existence of URAT1-like uric acid excretion mechanism in the salivary gland. The purpose of this study was to elucidate the uric acid excretion mechanism in salivary gland tissues using rabbit anti-human OAT1-4 and URAT1 polyclonal antibodies with EnVision(™) system.
In the salivary gland, OAT1 was expressed in ductal cells. OAT2 was found in both ductal cells and serous acinar cells and weak expression was also observed in several nuclei. OAT3 expression was observed in serous acinar cells and nuclei and OAT4 was expressed only in ductal cells. URAT1 expression was observed in the cytoplasm of ductal cells and strong punctuate staining was seen in part of the supra-nuclear cytoplasm. The number of cells expressing URAT1 was smaller compared with OATs. In the kidney, however, OAT1-4 and URAT1 were strongly expressed on proximal renal tubules.
The present study confirmed the existence of OAT1-4 and URAT1 in the salivary gland. These results may support the previous speculation that benzbromarone inhibits URAT1 to block uric acid reabsorption in the salivary gland, resulting in higher salivary uric acid levels than serum levels.
尿酸、有机酸和药物等各种物质都通过肾脏中的有机阴离子转运体(OATs)进行转运。此外,OAT 家族的一个成员,尿酸转运蛋白 1(URAT1),参与了尿酸从肾小管的重吸收。苯溴马隆通过抑制 URAT1 来阻断尿酸的重吸收。
我们的研究小组之前观察到服用苯溴马隆的患者唾液中的尿酸水平高于血清水平,并报告了唾液腺中可能存在类似 URAT1 的尿酸排泄机制。本研究旨在使用兔抗人 OAT1-4 和 URAT1 多克隆抗体结合 EnVision(™)系统,阐明唾液腺组织中的尿酸排泄机制。
在唾液腺中,OAT1 在导管细胞中表达。OAT2 存在于导管细胞和浆液性腺泡细胞中,在几个核中也观察到弱表达。OAT3 表达于浆液性腺泡细胞和核中,OAT4 仅在导管细胞中表达。URAT1 表达于导管细胞的细胞质中,部分核上细胞质中可见强烈的点状染色。表达 URAT1 的细胞数量比 OATs 少。然而,在肾脏中,OAT1-4 和 URAT1 在上皮细胞中强烈表达。
本研究证实了 OAT1-4 和 URAT1 在唾液腺中的存在。这些结果可能支持之前的推测,即苯溴马隆通过抑制 URAT1 阻断唾液腺中的尿酸重吸收,导致唾液中的尿酸水平高于血清水平。