Stimulation of phosphate transport in the proximal tubule by metabolic substrates

1984 ◽  
Vol 247 (4) ◽  
pp. F582-F587 ◽  
Author(s):  
S. R. Gullans ◽  
P. C. Brazy ◽  
L. J. Mandel ◽  
V. W. Dennis
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Initial Rate ◽  
Tricarboxylic Acid Cycle ◽  
Phosphate Transport ◽  
Glucose Absorption ◽  
Metabolic Substrates ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Stimulation Of

Studies of phosphate transport in the proximal tubule have recently focused on interactions with cellular metabolism. The present studies demonstrate that two fatty acids, valerate and butyrate, and two tricarboxylic acid cycle intermediates, succinate and malate, stimulate net phosphate transport in the rabbit proximal tubule by 34-117%. Valerate had no effect on the total uptake of inorganic [32P]phosphate into suspensions of proximal tubules but did enhance the initial rate of influx. Net fluid transport was unaffected by these substrates although glucose absorption increased by 10-15% following the addition of either valerate or succinate. Since valerate, butyrate, and succinate are known to stimulate gluconeogenesis and respiration, we evaluated the role of gluconeogenesis in the stimulation of phosphate transport. The addition of 3-mercaptopicolinate (1 mM), an inhibitor of gluconeogenesis, did not alter phosphate transport, nor did it prevent the valerate-induced stimulation of phosphate transport. We conclude that valerate, butyrate, succinate, and malate enhance phosphate transport by the proximal convoluted tubule. This action appears to be unrelated to effects on gluconeogenesis and may be related to close links between phosphate transport and oxidative metabolism.

Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates

1996 ◽  
Vol 271 (3) ◽  
pp. F717-F722
Author(s):  
G. Bajaj ◽  
M. Baum
Keyword(s):  
Oxygen Consumption ◽  
Proximal Tubule ◽  
Tricarboxylic Acid Cycle ◽  
Dimethyl Ester ◽  
Proximal Tubules ◽  
Intracellular Atp ◽  
Metabolic Substrates ◽  
Rate Of Oxygen Consumption ◽  
Intracellular Phosphate

Intracellular cystine loading by use of cystine dimethyl ester (CDME) results in a generalized inhibition in proximal tubule transport due, in part, to a decrease in intracellular ATP. The present study examined the importance of phosphate and metabolic substrates in the proximal tubule dysfunction produced by cystine loading. Proximal tubule intracellular phosphorus was 1.8 +/- 0.1 in control tubules and 1.1 +/- 0.1 nmol/mg protein in proximal tubules incubated in vitro with CDME P < 0.001). Infusion of sodium phosphate in rabbits and subsequent incubation of proximal tubules with a high-phosphate medium attenuated the decrease in proximal tubule respiration and prevented the decrease in intracellular ATP with cystine loading. Tricarboxylic acid cycle intermediates have been shown to preserve oxidative metabolism in phosphate-depleted proximal tubules. In proximal tubules incubated with either 1 mM valerate or butyrate, there was a 42 and 34% reduction (both P < 0.05) in the rate of oxygen consumption with cystine loading. However, tubules incubated with 1 mM succinate or citrate had only a 13 and 14% P = NS) reduction in the rate of oxygen consumption, respectively. These data are consistent with a limitation of intracellular phosphate in the pathogenesis of the proximal tubule dysfunction with cystine loading.

Increased fluid absorption and cell volume in isolated rabbit proximal straight tubules after in vivo DOCA administration

1981 ◽  
Vol 241 (5) ◽  
pp. F502-F508 ◽  
Author(s):  
M. A. Knepper ◽  
M. B. Burg
Keyword(s):  
Proximal Tubule ◽  
Cell Volume ◽  
Fluid Transport ◽  
Sodium Intake ◽  
Plasma Concentrations ◽  
Dietary Sodium ◽  
Fluid Absorption ◽  
Direct Stimulation ◽  
Stimulation Of

To investigate whether mineralocorticoids affect the intrinsic capacity of the proximal tubule to absorb sodium and fluid, rabbits were chronically treated a number of ways to systematically vary plasma concentrations of mineralocorticoid hormones. The rate of fluid absorption and tubule dimensions were measured in superficial S2 segments from these rabbits. Chronic administration of deoxycorticosterone acetate (DOCA) was associated with a 67% increase in fluid absorption and a 29% increase in cell volume per unit tubule length. However, neither adrenalectomy nor low sodium diet significantly affected either fluid absorption or cell volume. Furthermore, marked dietary sodium restriction prevented the response to DOCA. We conclude that the DOCA-induced increases in fluid absorption and cell volume do not result from a direct stimulation of the proximal tubular cells by the steroid but more likely are responses to systemic effects of DOCA administration that are dependent on the level of sodium intake. Thus, we find no evidence for a direct mineralocorticoid stimulation of sodium and fluid transport by the S2 portion of the proximal tubule.

Intracellular pH regulation in rabbit S3 proximal tubule: basolateral Cl-HCO3 exchange and Na-HCO3 cotransport

1990 ◽  
Vol 258 (2) ◽  
pp. F371-F381 ◽  
Author(s):  
N. L. Nakhoul ◽  
L. K. Chen ◽  
W. F. Boron
Keyword(s):  
Proximal Tubule ◽  
Intracellular Ph ◽  
Initial Rate ◽  
Ph Regulation ◽  
Basolateral Membrane ◽  
Intracellular Ph Regulation ◽  
S3 Segment ◽  
Absorbance Spectra ◽  
Rule Out

We studied the role of basolateral HCO3- transport in the regulation of intracellular pH (pHi) in the isolated perfused S3 segment of the rabbit proximal tubule. pHi was calculated from absorbance spectra of the pH-sensitive dye dimethylcarboxyfluorescein. Solutions were normally buffered to pH 7.4 at 37 degrees C with 25 mM HCO3- 5% CO2. pHi fell by approximately 0.17 when luminal [HCO3-] was lowered to 5 mM at fixed PCO2 (i.e., reducing pH to 6.8) but by approximately 0.42 when [HCO3-] in the bath (i.e., basolateral solution) was lowered to 5 mM. The pHi decrease elicited by reducing bath [HCO3-] was substantially reduced by removal of Cl- or Na+, suggesting that components of basolateral HCO3- transport are Cl- and/or Na+ dependent. We tested for the presence of basolateral Cl-HCO3 exchange by removing bath Cl-. This caused pHi to increase by approximately 0.23, with an initial rate of approximately 100 X 10(-4) pH/s. Although the initial rate of this pHi increase was not reduced by removing Na+ bilaterally, it was substantially lowered by the nominal removal of HCO3- from bath and lumen or by the addition of 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) to the bath. The results thus suggest that a Na-independent Cl-HCO3 exchanger is present at the basolateral membrane. We tested for the presence of basolateral Na-HCO3 cotransport by removing bath Na+. This caused pHi to fall reversibly by approximately 0.26 with initial rates of pHi decline and recovery being approximately 30 and approximately 41 X 10(-4) pH/s, respectively. Although the bilateral removal of Cl- had no effect on these rates, the nominal removal of HCO3- or the presence of DIDS substantially slowed the pHi changes. Thus, in addition to a Cl-HCO3 exchanger, the basolateral membrane of the S3 proximal tubule also appears to possess a Na-HCO3 cotransport mechanism. The data do not rule out the possibility of other basolateral HCO3- transporters.

scholarly journals Glutamine Addiction and Therapeutic Strategies in Lung Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 252 ◽  
Author(s):  
Karolien Vanhove ◽  
Elien Derveaux ◽  
Geert-Jan Graulus ◽  
Liesbet Mesotten ◽  
Michiel Thomeer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tricarboxylic Acid Cycle ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Production Networks ◽  
Tricarboxylic Acid Cycle Intermediates

Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.

Antegrade and retrograde fluid transport through the vas deferens

1995 ◽  
Vol 269 (5) ◽  
pp. R1197-R1203
Author(s):  
K. Kihara ◽  
K. Sato ◽  
M. Ando ◽  
H. Azuma ◽  
H. Oshima
Keyword(s):  
Fluid Transport ◽  
Vas Deferens ◽  
Ejaculatory Duct ◽  
Intraluminal Pressure ◽  
Muscle Tonus ◽  
Sperm Transport ◽  
Mode Of Transport ◽  
Seminal Emission ◽  
Stimulation Of

Intraluminal pressure of the seminal tract at seminal emission from the ejaculatory duct and the mode of transport of cauda epididymal contents were investigated to explore the mechanism of sperm transport. Direct electrical stimulation of any site of the cauda epididymis and vas deferens, which generated nerve-transmitted muscle contraction, caused elevation of the intraluminal pressure only at the cauda epididymis, whereas stimulation of the testis, caput, and corpus epididymis caused no response. The dye instilled in the cauda was emitted into the urethra during the stimulation. Shortly after discontinuation of the stimulation, retrograde movement of residual dye in the vas resulted in its ultimate reentry into the cauda epididymis. Significant decrease of the muscle tonus just after contraction was observed at the cauda. Distension of the wall of the vas generated elevation of the intraluminal pressure only at the site distended. The above results indicate the presence of rapid antegrade and retrograde movement of the sperm and the crucial role of the cauda epididymis on the sperm transport.

Glucocorticoids stimulate Na+/H+ antiporter in OKP cells

1993 ◽  
Vol 264 (6) ◽  
pp. F1027-F1031 ◽  
Author(s):  
M. Baum ◽  
A. Cano ◽  
R. J. Alpern
Keyword(s):  
Proximal Tubule ◽  
Intracellular Ph ◽  
Direct Effect ◽  
Initial Rate ◽  
Time Dependent ◽  
Affinity Constant ◽  
Maximal Velocity ◽  
Hemodynamic Changes ◽  
Acid Load ◽  
Stimulation Of

Previous studies have demonstrated that systemic administration of glucocorticoids stimulates proximal tubule acidification in part by increasing Na+/H+ antiporter activity; however, these studies could not exclude the possibility that changes in Na+/H+ antiporter activity were secondary to glucocorticoid-induced hemodynamic changes. The present study examined the effect of dexamethasone on Na+/H+ antiporter activity in quiescent OKP cells. Na+/H+ antiporter activity was assayed as the initial rate of Na(+)-dependent pH recovery from an acid load. Intracellular pH was measured using the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Dexamethasone produced a dose- and time-dependent stimulation of Na+/H+ antiporter activity in OKP cells. Dexamethasone produced a 24% stimulation in Na+/H+ antiporter activity at 10(-9) M and an approximately 40% stimulation of Na+/H+ antiporter activity at both 10(-8) and 10(-6) M. The effect of 10(-6) M dexamethasone was seen within 4 h of incubation and was due to an increase in maximal velocity (Vmax, 3.03 vs. 1.79 pH units/min) with no change in the affinity constant for sodium (KNa, 47.2 vs. 42.0 mM). The stimulatory effect of dexamethasone on Na+/H+ antiporter activity was blocked by cycloheximide and was not observed with 10(-8) M aldosterone. These data demonstrate a direct effect of glucocorticoids to stimulate Na+/H+ antiporter activity in OKP cells.

scholarly journals Induction of Methyl Tertiary Butyl Ether (MTBE)-Oxidizing Activity in Mycobacterium vaccae JOB5 by MTBE

2004 ◽  
Vol 70 (2) ◽  
pp. 1023-1030 ◽  
Author(s):  
Erika L. Johnson ◽  
Christy A. Smith ◽  
Kirk T. O'Reilly ◽  
Michael R. Hyman
Keyword(s):  
Culture Medium ◽  
Tricarboxylic Acid Cycle ◽  
Butyl Alcohol ◽  
Butyl Ether ◽  
Tertiary Butyl ◽  
Mycobacterium Vaccae ◽  
Culture Growth ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Product Accumulation

ABSTRACT Alkane-grown cells of Mycobacterium vaccae JOB5 cometabolically degrade the gasoline oxygenate methyl tertiary butyl ether (MTBE) through the activities of an alkane-inducible monooxygenase and other enzymes in the alkane oxidation pathway. In this study we examined the effects of MTBE on the MTBE-oxidizing activity of M. vaccae JOB5 grown on diverse nonalkane substrates. Carbon-limited cultures were grown on glycerol, lactate, several sugars, and tricarboxylic acid cycle intermediates, both in the presence and absence of MTBE. In all MTBE-containing cultures, MTBE consumption occurred and tertiary butyl alcohol (TBA) and tertiary butyl formate accumulated in the culture medium. Acetylene, a specific inactivator of alkane- and MTBE-oxidizing activities, fully inhibited MTBE consumption and product accumulation but had no other apparent effects on culture growth. The MTBE-dependent stimulation of MTBE-oxidizing activity in fructose- and glycerol-grown cells was saturable with respect to MTBE concentration (50% saturation level = 2.4 to 2.75 mM), and the onset of MTBE oxidation in glycerol-grown cells was inhibited by both rifampin and chloramphenicol. Other oxygenates (TBA and tertiary amyl methyl ether) also induced the enzyme activity required for their own degradation in glycerol-grown cells. Presence of MTBE also promoted MTBE oxidation in cells grown on organic acids, compounds that are often found in anaerobic, gasoline-contaminated environments. Experiments with acid-grown cells suggested induction of MTBE-oxidizing activity by MTBE is subject to catabolite repression. The results of this study are discussed in terms of their potential implications towards our understanding of the role of cometabolism in MTBE and TBA biodegradation in gasoline-contaminated environments.

scholarly journals Novel developments in differentiating the role of renal and intestinal sodium hydrogen exchanger 3

2016 ◽  
Vol 311 (6) ◽  
pp. R1186-R1191 ◽  
Author(s):  
Jessica A. Dominguez Rieg ◽  
Samantha de la Mora Chavez ◽  
Timo Rieg
Keyword(s):  
Proximal Tubule ◽  
Knockout Mice ◽  
Collecting Duct ◽  
Phosphate Transport ◽  
Thick Ascending Limb ◽  
Sodium Hydrogen Exchanger ◽  
Novel Drug ◽  
Therapeutic Considerations ◽  
Insight Into

The Na+/H+ exchanger isoform 3 (NHE3) facilitates Na+ absorption and H+ secretion and is expressed in the intestine, proximal tubule, and thick ascending limb of the kidney. While the function of NHE3 for Na+ and [Formula: see text](re)absorption has been defined using conventional NHE3 knockout mice (NHE3−/−), the recent generation of conditional NHE3 knockout mice started to give critical new insight into the role of this protein by allowing for temporal and spatial control of NHE3 expression. For example, in contrast to NHE3−/− mice, knockout of NHE3 in the S1 and S2 segments of the proximal tubule or along the entire tubule/collecting duct does not cause any lethality. Nonabsorbable NHE3 inhibitors have been developed, and preclinical as well as clinical trials indicate possible pharmacological use in fluid overload, hypertension, chronic kidney disease, hyperphosphatemia, and constipation. Some of the therapeutic considerations seem to be directly related to the pharmacodynamic properties of these drugs; however, little is known about the effects of these nonabsorbable NHE3 inhibitors on intestinal phosphate transport and the mechanisms so far remain elusive. This review focuses on novel findings of NHE3 in the intestine and the kidney as well as novel drug developments targeting NHE3.

Acid extrusion in S3 segment of rabbit proximal tubule. I. Effect of bilateral CO2/HCO3-

1995 ◽  
Vol 268 (2) ◽  
pp. F179-F192 ◽  
Author(s):  
L. K. Chen ◽  
W. F. Boron
Keyword(s):  
Steady State ◽  
Proximal Tubule ◽  
Initial Rate ◽  
Iodoacetic Acid ◽  
Buffering Power ◽  
Acid Load ◽  
S3 Segment ◽  
Series Of Experiments ◽  
Acid Extrusion ◽  
Stimulation Of

Monitoring the absorbance spectra of the pH-sensitive dye dimethylcarboxyfluorescein, we studied intracellular pH (pHi) regulation in the isolated perfused S3 segment of rabbit proximal tubule. To explain a previous observation, that steady-state pHi is higher in the presence than in the absence of CO2/HCO3- (N. L. Nakhoul, L. K. Chen, and W. F. Boron. J. Gen. Physiol. 102: 1171-1205, 1993), we examined the effect of bilateral (i.e., luminal and basolateral) CO2/HCO3- on the acid extrusion processes responsible for recovery of pHi from acid loads. To compute fluxes from rates of pHi change, we determined the pHi dependence of intrinsic intracellular buffering power, which was approximately 50 mM/pH at pHi 6.5 and fell linearly to approximately 20 mM at pHi 7.4. In one series of experiments, we monitored the rate of pHi recovery from an acid load imposed by an NH4+/NH3 prepulse. Over a broad range of pHi values, total net acid extrusion was approximately four times higher in bilateral presence of CO2/HCO3- than in its absence. In a second group of experiments, which were designed to determine the effect of CO2/HCO3- on luminal Na+/H+ exchange, we monitored the rate of pHi recovery elicited by adding Na+ back to only the lumen, after first removing Na+ bilaterally. Initial rate of luminal Na(+)-dependent net acid extrusion in presence of CO2/HCO3- was approximately 229 microM/s (pHi 6.92), approximately 1.8 times higher than the flux of approximately 127 microM/s (P < 0.005) obtained in absence of CO2/HCO3- (pHi 6.66). CO2/HCO3- alkali-shifted the flux vs. pHi relationship by 0.3-0.4 pH units. In a final series of experiments, we examined the effect of CO2/HCO3- on the Na(+)-independent alkalinization that follows the rapid, initial acidification elicited by bilateral Na+ removal. In the presence of CO2/HCO3-, lag time for initiation of the Na(+)-independent alkalinization was only approximately 36 vs. approximately 211 s (P < 0.002) in absence of CO2/HCO3-. Also, Na(+)-independent net acid extrusion rate was approximately two to three times higher in presence than in absence of CO2/HCO3- at comparable pHi. This Na(+)-independent acid extrusion was insensitive to N-ethylmaleimide (2 mM), but was inhibited approximately 94% by efforts to deplete intracellular ATP (i.e., removal of glucose and amino acids, plus addition of 2 mM cyanide and 10 mM iodoacetic acid). Stimulation of luminal Na+/H+ exchange and Na(+)-independent acid extrusion appears to be the major, if not the entire, explanation for the higher steady-state pHi caused by bilateral addition of CO2/HCO3-.

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