Immunohistochemical studies of organic anion transporters and urate transporter 1 expression in human salivary gland

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.