Expression of the Na+/myo-inositol cotransporter in the juxtaglomerular region

Abstract

Myo-inositol is a major compatible osmolyte in the renal medulla and is accumulated in cells under hypertonic conditions by uptake via a Na+/myo-inositol cotransporter (SMIT). SMIT is regulated by extracellular osmolarity at the transcription level. We investigated localization of SMIT in rat kidney by immunohistochemical staining using an anti-SMIT-antibody raised against a synthetic peptide corresponding to part of SMIT and by in situ hybridization. SMIT protein localized predominantly to the basolateral membranes of cells of the thick ascending limb of Henle (TAL) and inner medullary collecting duct (IMCD). Macula densa (MD) cells, identified as the Tamm-Horsfall-protein (THP)-unreactive cells surrounded by THP-reactive TAL cells, also stained for anti-SMIT. In situ hybridization yielded the intense SMIT signals in the TAL and IMCD and also in the juxtaglomerular (JG) region. Prior loading of the animal with a high concentration of NaCl rapidly induced SMIT mRNA; furosemide down-regulated it. The high level of SMIT expression suggests that MD cells are exposed to hypertonicity at the basolateral surface. Because SMIT expression seemed to be proportional to the magnitude of NaCl reabsorption, it may be a good marker for examination of the tubuloglomerular feedback mechanism in vivo.