Renal Tubular Phosphate Reabsorption

FIGURE 7-3

Renal tubular reabsorption of phosphorus. Most of the inorganic phosphorus in serum is ultrafilterable at the level of the glomerulus. At physiologic levels of serum phosphorus and during a normal dietary phosphorus intake, most of the filtered phosphorous is reabsorbed in the proximal convoluted tubule (PCT) and proximal straight tubule (PST). A significant amount of filtered phosphorus is also reabsorbed in distal segments of the nephron [7,9,10]. CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.

Lumen

Gluconeogenesis Glycolysis

Blood Pi

Blood Pi

Gluconeogenesis Glycolysis

Oxidative phosphorylation

-65mV -65mV

Oxidative phosphorylation

-65mV -65mV

FIGURE 7-4

Cellular model for renal tubular reabsorption of phosphorus in the proximal tubule. Phosphate reabsorption from the tubular fluid is sodium gradient-dependent and is mediated by the sodium gradient-dependent phosphate transport (Na-P( cotransport) protein located on the apical brush border membrane. The sodium gradient for phosphate reabsorption is generated by then sodium-potassium adenosine triphosphatase (Na-K ATPase) pump located on the basolateral membrane. Recent studies indicate that the Na-P( cotransport system is electrogenic [8,11]. ADP—adenosine diphosphate; An—anion.

Cellular model of proximal tubule P.-reabsorption

Blood

Parathyroid hormone dietary P( content

Parathyroid hormone dietary P( content hpo;

hpo;

3Na+

3Na+

Na+

—>-

Celluar model of proximal tubular phosphate reabsorption. Major physiologic determinants of renal tubular phosphate reabsorption are alterations in parathyroid hormone activity and alterations in dietary phosphate content. The regulation of renal tubular phosphate reabsorption occurs by way of alterations in apical membrane sodium-phosphate (Na-Pj) cotransport 3Na+-HPO2~4 activity [11-14].

FACTORS REGULATING RENAL PROXIMAL TUBULAR PHOSPHATE REABSORPTION

Decreased transport

Increased transport

High phosphate diet Parathyroid hormone and parathyroid-

hormone-related protein Glucocorticoids Chronic metabolic acidosis Acute respiratory acidosis Aging Calcitonin

Atrial natriuretic peptide Fasting Hypokalemia Hypercalcemia Diuretics Phosphatonin

Low phosphate diet Growth hormone Insulir

Thyroid hormone 1,25-dihydroxy-vitamin D3 Chronic metabolic alkalosis High calcium diet High potassium diet Stanniocalcin

FIGURE 7-6

Factors regulating renal proximal tubular phosphate reabsorption.

A

O o

G

D

FIGURE 7-7 (see Color Plate)

FIGURE 7-7 (see Color Plate)

Effects of a diet low in phosphate on renal tubular phosphate reabsorption in rats. A, Chronic high Pi diet. B, Acute low Pi diet. C, Colchicine and high Pi diet. D, Colchicine and low Pi diet. In response to a low phosphate diet, a rapid adaptive increase occurs in the sodium-phosphate (Na-Pj) cotransport activity of the proximal tubular apical membrane (A, B). The increase in Na-Pi cotransport activity is mediated by rapid upregulation of the type II Na-Pi cotransport protein, in the absence of changes in Na-Pi messenger RNA (mRNA) levels. This rapid upregulation is dependent on an intact microtubular network because pretreatment with colchicine prevents the upregulation of Na-Pi cotrans-port activity and Na-Pi protein expression (C, D). In this immunofluorescence micrograph, the Na-Pi protein is stained green (fluorescein) and the actin cytoskeleton is stained red (rhodamine). Colocalization of green and red at the level of the apical membrane results in yellow color [14].

FIGURE 7-8 (see Color Plate)

Effects of parathyroid hormone (PTH) on renal tubular phosphate reabsorption in rats. In response to PTH administration to parathyroidectomized rats, a rapid decrease occurs in the sodium-phosphate (Na-Pi) cotransport activity of the proximal tubular apical membrane. The decrease in Na-Pi cotransport activity is mediated by rapid downregulation of the type II Na-P( cotransport protein. In this immunofluores-cence micrograph, the Na-Pi protein is stained green (fluorescein) and the actin cytoskeleton is stained red (rhodamine). Colocalization of green and red at the level of the apical membrane results in yellow color [13]. A, parathyroidectomized (PTX) effects. B, effects of PTX and PTH.

Phosphate Absorption Kidney
FIGURE 7-9

Renal cholesterol content modulates renal tubular phosphate reabsorption. In aged rats versus young rats and rats fed a diet high in phosphate versus a diet low in phosphate, an inverse correlation exists between the brush border membrane (BBM) cholesterol content (A) and Na-P( cotransport activity (B). Studies in isolated BBM vesicles and recent studies in opossum kidney cells grown in culture indicate that direct alterations in cholesterol content per se modulate Na-Pj cotransport activity [15]. CON—controls.

FIGURE 7-10

Renal glycosphingolipid content modulates renal tubular phosphate reabsorption. In rats treated with dexamethasone (DEX) and in rats fed a potassium-deficient diet, an inverse correlation exists between brush border membrane (BBM) glucosylceramide (GluCer)—and ganglioside GM3, content and Na-Pi cotransport activity. Treatment of rats with a glucosylceramide synthase inhibitor PDMP lowers BBM glucosylceramide content (A) and increases Na-Pi cotransport activity (B) [16].

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