Kinetic studies on the stimulation of Na+−H+ exchange activity in renal brush border membranes isolated from thyroid hormone-treated rats

Abstract

Na+-H+ exchange activity in renal brush border membrane vesicles isolated from hyperthyroid rats was increased. When examined as a function of [Na+], treatment altered the initial rate of Na+ uptake by increasing Vm (hyperthyroid, 18.9 +/- 1.1 nmol Na+ X mg-1 X 2 sec-1; normal, 8.9 +/- 0.3 nmol Na+ X mg-1 X 2 sec-1), and not the apparent affinity KNa+ (hyperthyroid, 7.3 +/- 1.7 mM; normal, 6.5 +/- 0.9 mM). When examined as a function of [H+] and at a subsaturating [Na+] (1 mM), hyperthyroidism resulted in the proportional increase in Na+ uptake at every intravesicular pH measured. A positive cooperative effect on Na+ uptake was found with increased intravesicular acidity in vesicles from both normal and hyperthyroid rats. When the data were analyzed by the Hill equation, it was found that hyperthyroidism did not change the n (hyperthyroid, 1.2 +/- 0.06; normal, 1.2 +/- 0.07) or the [H+]0.5 (hyperthyroid, 0.39 +/- 0.08 microM; normal, 0.44 +/- 0.07 microM) but increased the apparent Vm (hyperthyroid, 1.68 +/- 0.14 nmol Na+ X mg-1 X 2 sec-1; normal 0.96 +/- 0.10 nmol Na+ X mg-1 X 2 sec-1). The uptake of Na+ in exchange for H+ in membrane vesicles from normal and hyperthyroid animals was not influenced by membrane potential. H+ translocation or debinding was rate limiting for Na+-H+ exchange since Na+-Na+ exchange activity was greater than Na+-H+ exchange activity. Hyperthyroidism caused a proportional increase and hypothyroidism caused a proportional decrease in Na+-Na+ and Na+-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormone stimulates the renal Na/H exchanger NHE3 by transcriptional activation

“…In both brush-border vesicles and OK cells, T 3 activates Na/H exchange by increasing its V max (18,30), a kinetic effect that is compatible with increased transporter protein abundance. To further define the mechanisms of the increase, we examined steady-state NHE3 mRNA and protein levels in response to T 3 in OK cells.…”

“…A significant portion of proximal tubule NaCl and NaHCO 3 transport is mediated by apical membrane Na/H exchange (24,25). Na/H exchange activity in renal cortical apical membrane vesicles is increased in hyperthyroid and decreased in hypothyroid animals (18,19). Although the effect on apical membrane Na/H exchange may be mediated in part by changes in glomerular filtration rate, systemic hemodynamic and/or neurohumoral changes (17), a direct effect of thyroid hormone on the maximum velocity (V max ) of the Na/H exchanger has been demonstrated in a cell culture model of the proximal tubule, the opossum kidney (OK) cell (30).…”

Overexpression of csk inhibits acid-induced activation of NHE-3.

“…Chronic metabolic acidosis causes an increase in the activity of the renal proximal tubule apical membrane Na+/H+ antiporter that persists after the transporter is removed from the acidotic environment (1)(2)(3). This effect represents a direct effect of pH, in that chronic incubation of cultured proximal tubule cells in acid medium leads to increases in the activities and mRNA abundance of two Na+/H+-antiporter isoforms, NHE-1 and NHE-3 (Na+/H+ exchangers 1 and 3) (4-7).…”

Identification of a small Na+/H+ exchanger‐like message in the rabbit myocardium

“…This message increases both with &hernia and during reperfusion following ischemia. The increased message could presumably lead to increased production of the protein, similar to what has been suggested in other tissues for the Nat/H+ exchanger [4][5][6][7]10,17]. If the SLIF message encodes for a form of the Na'/H' exchanger, it could play a signifcant role in contributing to reperfusion arrhythmias in the myocardium [2,3].…”

“…A number of studies have suggested that the gene encoding for the Na+/H' exchanger can be influenced by environmental factors which affect intracellular pH (4)(5)(6)(7)(8). The level of Na'/H' exchange activity (V,) is increased by external stimuli such as glucocorticoids and acidosis.…”