Thyroid hormones increase Na+-H+ exchange activity in renal brush border membranes.

Abstract

Na+-H' exchange activity, i.e., amiloridesensitive Na' and H' flux, in renal proximal tubule brush border (luminal) membrane vesicles was increased in the hyperthyroid rat and decreased in the hypothyroid rat, relative to the euthyroid animal. A positive correlation was found between Na'-H' exchange activity and serum concentrations of thyroxine (T4) and triiodothyronine (T3). The thyroid status of the animal did not alter amiloride-insensitive Na' uptake.The rate of passive pH gradient dissipation was higher in membrane vesicles from hyperthyroid rats compared to the rate in vesicles from hypothyroid animals, a result which would tend to limit the increase in Na' uptake in vesicles from hyperthyroid animals. Na'-dependent phosphate uptake was increased in membrane vesicles from hyperthyroid rats; Na'-dependent D-glucose and L-proline uptakes were not changed by the thyroid status of the animal. The effect of thyroid hormones in increasing the uptake of Na' in the brush border membrane vesicle is consistent with the action of the hormones in enhancing renal Na+ reabsorption. Further, the regulation of transtubular Na+ flux has now been shown to be concomitant with modulation of the entry of Na' into the tubular cell across its luminal membrane, mediated by the exchange reaction, and with the previously reported control of the pumping of Na+ out of the cell across its basolateral membrane, mediated by the Na+,K+-ATPase.Thyroid hormones (thyroxine, T4; triiodothyronine, T3) have a significant role in controlling kidney growth and function. The hormones are important regulators of renal plasma flow, glomerular filtration rate, concentration and dilution of urine, oxygen consumption, and the reabsorption of phosphate, Ca2+, and Na+ (1, 2). Thyroid hormones stimulate Na+, K+-ATPase activity (3), and changes in renal Na+,K+-ATPase activity closely parallel alterations in net transport of Na+ (4). T3 is known to induce the synthesis of Na+, K+-ATPase (5). It also has been proposed that thyroid hormones augment renal Na+,K+-ATPase activity by an adaptive mechanism responding to changing resorptive Na+ loads (4). Both mechanisms, the induction of Na+ pump elements and the adaptive response to increased filtered Na+, could operate together in mediating the action of thyroid hormones on Na+ reabsorption (1). Another hypothesis, that thyroid hormones enhance the entry of Na+ from the filtrate to the tubular cell across the luminal membrane, merits consideration.Na+, at physiological concentrations, crosses the luminal brush border membrane of the proximal tubule mostly by Na+-H+ exchange (6, 7). The carrier mediates the electroneutral antiport of Na+ for H+, Na+ entering the cell as H+ migrates from cell to lumen (8-10). Amiloride at relatively high concentrations (Ki = 5 x 10-5M) competitively inhibits exchange activity (10). In contrast, the ouabainsensitive Na',K+-ATPase, which serves to pump Na' from cell to interstitium, is located on the basolateral membrane of the tubular cell (11).We have reported recently t...

Maturation of the Na+/H+antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

“…The thyroid hormone status was found to have a greater impact on Na + /H + antiporter activity in adult rats than we found in our neonatal rats (8,28). In agreement with our study, NHE3 mRNA abundance was comparable in both hypothyroid and euthyroid adult rats and was higher in hyperthyroid rats (3).…”

Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol.

“…At equilibrium (180 min), accumulation of 22Na was, however, similar in control and diabetic vesicles. As previously discussed (35,36), the latter finding indicates that diabetes did not influence average intravesicular volume and, therefore, the increased 22Na uptake at early time points (up to 3 min) could not be ascribed to altered vesicular size in these experiments. Since similar aliquots of membrane proteins were used in the transport experiments, this also rules out changes in vesicular number as being responsible for increased 22Na uptake observed in these experiments.…”

Cell pH in the rat proximal convoluted tubule. Regulation by luminal and peritubular pH and sodium concentration.

“…While studies in rabbit brush border membrane vesicles have found that the Na/H antiporter is very sensitive to amiloride (25,26), similar studies in rat brush border vesicles have found less sensitivity to amiloride (31,32). Based on the data of Kinsella and Sacktor (31), and of Sabolic and Burckhardt (32) in rat brush border membrane vesicles, one would predict that 2 mM amiloride in the presence of 75 meq/liter Na would inhibit Na/H exchange by 81% and 67%, respectively. These predictions are relatively similar to our finding that the rate of pH change after luminal sodium removal was inhibited by 81% by 2 mM amiloride.…”