Localization and rapid regulation of Na+/myo-inositol cotransporter in rat kidney.

Abstract

myo-Inositol, a major compatible osmolyte in renal medulla, is accumulated in several kinds of cells under hypertonic conditions via Na+/myo-inositol cotransporter (SMIT). To investigate the physiological role of the SMIT, we sought to determine its localization by in situ hybridization and its acute regulation by NaCl and furosemide administration. Northern analysis demonstrated that SMIT is strongly expressed in the medulla and at low levels in the cortex of kidney. Intraperitoneal injection of NaCI rapidly induced SMIT mRNA in both the cortex and medulla, and furosemide completely abolished this induction. In situ hybridization revealed that SMIT is predominantly present in the medullary and cortical thick ascending limbs of Henle's loop (TALH) and macula densa cells. Less intense signals were seen in the inner medullary collecting ducts (IMCD). NaCI loading increased the signals throughout the TALH, and furosemide reduced the signals. SMIT in the IMCD is less sensitive to these kinds of acute regulation. Thus, the distribution pattern of SMIT does not correspond to the corticomedullary osmotic gradient, and SMIT in the TALH and macula densa cells is regulated very rapidly. These results suggest that SMIT expression in TALH may be regulated by intracellular and/or peritubular tonicity close to the basolateral membrane, which is supposed to be proportional to the magnitude of NaCl reabsorption. (J. Clin. Invest. 1995.

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents

“…To extend this observation to an in vivo model, we subjected male Sprague-Dawley rats to 24 hours of water deprivation, a procedure that is known to increase urine osmolality (4,8,10,26,43) and renal medullary sodium concentration (4,42,43). As shown in Table 1, water deprivation resulted in a significant increase in urine osmolality (~40% increase over the baseline urine osmolality).…”

“…We have also demonstrated that hypertonicity increases expression of the type A natriuretic peptide receptor (NPR-A) (41), a guanylyl cyclase-linked receptor that binds both atrial natriuretic peptide (ANP) and the B-type natriuretic peptide (BNP), leading to an increase in renal excretion of sodium. Water deprivation leads to increased renal medullary sodium concentration (4,42,43). We reasoned that tonicity-dependent stimulation of Sgk1 and subsequent activation of NPR-A gene expression might be linked to the dehydration natriuresis described above.…”

Na+/myo-inositol transport is regulated by basolateral tonicity in Madin-Darby canine kidney cells.

“…In situ hybridization study indicated that SMIT predominantly expressed TALH (16), where a large transepithelial osmotic gradient exists (Fig. 4) (20).…”

“…Our previous report (15) showed that SMIT mRNA abundance was highest in the outer medulla rather than in the inner medulla, and a small but significant amount of SMIT mRNA was present in the cortex. SMIT mRNA in the cortex as well as that in the medulla was significantly induced by dehydration.…”

“…SMIT mRNA in the cortex as well as that in the medulla was significantly induced by dehydration. We have recently shown using in situ hybridization (16) that SMIT mRNA is predominantly present in the thick ascending limb of Henle's loop (TALH) and macula densa cells, and that NaCl loading rapidly increases the signals. Basal expression and magnitude of the induction by NaCl administration seemed to be uniform throughout the TALH as well as macula densa cells.…”