Metabolic Requirement for Inorganic Phosphate by the Rabbit Proximal Tubule

Abstract

A B S T R A C T These studies examine the effects of acute changes in the availability of inorganic phosphate on the function of isolated proximal renal tubules from rabbit kidney. We removed phosphate from the extracellular fluids and measured fluid absorption rates in isolated. perfused tubules and oxygen consumption rates in suspensions of cortical tubules. In proximal convoluted tubules, the selective removal of phosphate from the luminal fluid reduced fluid absorption rates from 1.11±0.12 to -0.01±0.08 nl/mmmin. This effect on fluid absorption was dependent on the presence of glucose transport and metabolism. The addition of phlorizin to the phosphate-free luminal fluid preserved fluid absorption rates (1.12±0.12 nl/ mm -min) as did the substitution of nonmetabolized a-methyl D-glucopyranoside for glucose (1.05±0.21 nl/mm min) or the addition of 2-deoxyglucose, an inhibitor of glycolysis, to the bathing medium (1.01±0.15 nl/mm -min). There was no effect on fluid absorption if phosphate was removed from the bath only. Additionally, removal of phosphate from the luminal fluid of proximal straight rather than convoluted tubules had no effect on fluid absorption rates. Oxygen consumption rates in suspensions of cortical tubules were reduced from 18.9±0.6 to 10.6±0.6 nmol O2/mg tubular protein * min by the removal of phosphate from the medium. This inhibition was prevented by the substitution of a-methyl D-glucopyranoside for glucose in the phosphate-free medium. The data indicate that under certain conditions, proximal convoluted tubules require the presence of phosphate in the luminal fluid to preserve tubular function. In the absence of intraluminal phosphate, glucose metabolism causes a reduction in both oxidative metab-

A perifusion loop‐gap resonator NMR probe for aerobic cell suspensions

“…The rate of disappearance was 60 nmol/ mglmin (equivalent to JaMG), indicating the nonmetabolized substrate was transported via open lumens. This rate compares favorably to the rate achieved using isolated perfused proximal tubules (74 nmol/mg/min, 16).…”

Characterization of the Early Ultrastructural and Biochemical Events Occurring in Dichloromethane Diphosphonate Nephrotoxicity

“…Availability of intracellular inorganic phosphate has been demonstrated to regulate energy metabolism by the cell as a potential injury mechanism (3). Transport of ClzMDP by a phosphate trap-sport mechanism could adversely influence intracellular phosphate availability.…”

The Fanconi syndrome of cystinosis: insights into the pathophysiology

“…Perfusion of proximal convoluted tubules with an ultrafiltrate-like solution 0.81 ± 0.14 -0. without phosphate resulted in a total inhibition of active transport [31]. When proximal tubules were perfused with an ultrafiltrate-like solution without glucose or with glucose and phlorizin, an inhibitor of glucose transport, active transport was the same as that measured in the presence of phosphate.…”

“…When proximal tubules were perfused with an ultrafiltrate-like solution without glucose or with glucose and phlorizin, an inhibitor of glucose transport, active transport was the same as that measured in the presence of phosphate. Similarly, the rate of proximal tubule oxygen consumption was impaired in the absence of phosphate in the incubation solution, only when glucose was present [31]. Glucose-induced inhibition in proximal tubule transport and oxygen consumption in the absence of phosphate is analogous to the Crabtree effect [33], where there is a glucose-dependent decrease in intracellular phosphate due to the accumulation of phosphorylated glycolytic intermediates.…”

“…The proximal tubule is dependent on phosphate to maintain active transport [31,32]. Perfusion of proximal convoluted tubules with an ultrafiltrate-like solution 0.81 ± 0.14 -0. without phosphate resulted in a total inhibition of active transport [31].…”