Effect of stevioside on PAH transport by isolated perfused rabbit renal proximal tubule

2000 ◽  
Vol 78 (9) ◽  
pp. 737-744 ◽  
Author(s):  
Promsuk Jutabha ◽  
Chaivat Toskulkao ◽  
Varanuj Chatsudthipong
Keyword(s):  
Proximal Tubule ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Tubular Function ◽  
Transepithelial Transport ◽  
Renal Tubules ◽  
Bathing Medium ◽  
Basolateral Side ◽  
Renal Tubular

Stevioside, a non-caloric sweetening agent, is used as a sugar substitute. An influence of stevioside on renal function has been suggested, but little is known about its effect on tubular function. Therefore, the present study was designed to explore the direct effect of stevioside on transepithelial transport of p-aminohippurate (PAH) in isolated S2 segments of rabbit proximal renal tubules using in vitro microperfusion. Addition of stevioside at a concentration of 0.45 mM to either the tubular lumen, bathing medium, or both at the same time had no effect on transepithelial transport of PAH. Similarly, a concentration of 0.70 mM (maximum solubility in the buffer) when present in the lumen, had no effect on PAH transport. However, this concentration in the bathing medium inhibited PAH transport significantly by about 25-35%. The inhibitory effect of stevioside was gradually abolished after it was removed from the bath. Addition of 0.70 mM stevioside to both lumen and bathing medium at the same time produced no added inhibitory effect. Stevioside at this concentration has no effect on Na+/K+-ATPase activity as well as cell ATP content. These findings suggest that stevioside, at a pharmacological concentration of 0.70 mM, inhibits transepithelial transport of PAH by interfering with the basolateral entry step, the rate-limiting step for transepithelial transport. The lack of effect of stevioside on transepithelial transport of PAH on the luminal side and its reversible inhibitory effect on the basolateral side indicate that stevioside does not permanently change PAH transport and should not harm renal tubular function at normal human intake levels.Key words: stevioside, p-aminohippurate, renal proximal tubule.

Abstract 503: Regulation of D5 Dopamine Receptor on Renalase Expression and Function in Rat Renal Proximal Tubule Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Shaoxing Wang ◽  
Pedro Jose ◽  
Chunyu Zeng
Keyword(s):  
Proximal Tubule ◽  
Dopamine Receptor ◽  
Sch 23390 ◽  
Mrna Level ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
And Function

The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies show the regulation of dopamine receptor on α 1 -adrenergic receptor function. Due to the regulation of renalase on sympathetic tone, we hypothesize that dopamine receptor, especially D 1 -like receptor, might regulate renalase in kidney. The effect of D 1 -like receptor on renalase expression and function was checked in immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). It resulted that D 1 -like receptor agonist, fenoldopam (10 -7 -10 -5 M), increased renalase protein expression and function in WKY RPT cells, in contrast, decreased it in SHR cells. These effects were blocked by D 1 -like receptor antagonist SCH 23390 (10 -6 M). Fenoldopam increased renalase mRNA level in WKY RPT cells, but not in SHR cells. Fenoldopam increased the degradation of renalase protein in both WKY and SHR cells. However, the degradation degree was higher in SHR cells than in WKY cells. The regulation of D 1 -like receptor on renalase was mainly via D 5 receptor, because inhibition of D 5 , not D 1 receptor, by antisense blocked inhibitory effect of D 1 -like receptor on renalase in WKY cells. Moreover, inhibition of PKC, by PKC inhibitor 19-31, blocked the effect of fenoldopam on renalase expression; stimulation of PKC, by PKC agonist (PMA), inhibited renalase expression and function, indicating that PKC is involved in the process. Consistent with the in-vitro study, renalase expression was lower in kidney from SHRs than in WKY rats. It indicated that D 1 -like receptor, via D 5 receptor, regulates renalase expression and function in RPT cells, aberrant regulation of D 5 receptor on renalase might be involved in the pathogenesis of hypertension.

Isolated perfused Ambystoma proximal tubule: hydrodynamics modulates ultrastructure

1987 ◽  
Vol 252 (6) ◽  
pp. F1129-F1147
Author(s):  
S. Tripathi ◽  
E. L. Boulpaep ◽  
A. B. Maunsbach
Keyword(s):  
Hydrostatic Pressure ◽  
Proximal Tubule ◽  
Axial Flow ◽  
Transepithelial Transport ◽  
Ambystoma Tigrinum ◽  
Renal Tubules ◽  
Pressure Gradients ◽  
Pressure Sensing ◽  
Cell Height

A method using a pressure-sensing servo-pipette is described for measuring downstream transepithelial pressure within isolated renal tubules perfused at flow rates designed to keep luminal solution composition constant. The hydrodynamics of in vitro microperfusion of isolated proximal tubules of Ambystoma tigrinum was varied and different states of transepithelial hydrostatic pressure difference, axial tubule flow, and transepithelial transport were correlated with epithelial ultrastructure. Tubules analyzed by ultrastructural morphometry were as follows: unperfused with and without ouabain, perfused single-end cannulated with and without ouabain, and perfused double-end cannulated tubules incubated in substrate Ringer. The results indicate that proximal tubule fine structure is well preserved for more than 3 h in unperfused and perfused tubules. Small transepithelial hydrostatic pressure gradients (less than 162 Pa) increase tubule diameters and decrease cell height without changing volumes of the cells, lateral intercellular spaces (LIS), or the basal extracellular labyrinth (BEL). Pressure gradients of 271 Pa have no further effect on tubule diameters or cell height, but significantly reduce volumes of LIS and BEL. Transport inhibition and axial flow changes have minor structural effects. This study demonstrates a close dependence of tubule ultrastructure on hydrodynamic conditions and provides guidelines for optimizing the latter during perfusion of isolated renal tubules.

Nephrotoxicity Testing In Vitro: The Current Situation

1997 ◽  
Vol 25 (5) ◽  
pp. 497-503
Author(s):  
Jean-Paul Morin ◽  
Marc E. De Broe ◽  
Walter Pfaller ◽  
Gabriele Schmuck
Keyword(s):  
Proximal Tubule ◽  
Culture Media ◽  
Task Force ◽  
Primary Cultures ◽  
Phenotypic Expression ◽  
Transepithelial Transport ◽  
Specific Cell ◽  
Proximal Tubule Cells ◽  
Tubule Cells

An ECVAM task force on nephrotoxicity has been established to advise, in particular, on the follow-up to recommendations made in the ECVAM workshop report on nephrotoxicity testing in vitro. Since this workshop was held, in 1994, there have been several improvements in the techniques used. For example, the duration of renal slice viability, and the maintenance of functional activities in slices, have been improved by using dynamic incubation systems with higher oxygen tensions and more-appropriate cell culture media. Highly differentiated primary cultures of pig, human and rabbit proximal tubule cells have been established by using specific cell isolation procedures and/or selective culture media. To date, the most comparable phenotypic expression and transepithelial transport capacities to proximal tubules in vivo have been obtained with primary cultures of rabbit proximal tubule cells which are grown on bicompartmental supports; in this system, transepithelial substrate gradients are generated and the transepithelial transport of both organic anions and cations is highly active. This in vitro system has been selected by ECVAM for further evaluation and prevalidation. Industrial needs in the area of nephrotoxicity testing have been identified, and recommendations are made at the end of this report concerning possible future initiatives.

scholarly journals Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells

2009 ◽  
Vol 296 (2) ◽  
pp. F355-F361 ◽  
Author(s):  
Rochelle Cunningham ◽  
Rajatsubhra Biswas ◽  
Marc Brazie ◽  
Deborah Steplock ◽  
Shirish Shenolikar ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Signaling Pathways ◽  
Phosphate Transport ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Phosphate Cotransport ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells ◽  
Sodium Phosphate Cotransport

The present experiments were designed to detail factors regulating phosphate transport in cultured mouse proximal tubule cells by determining the response to parathyroid hormone (PTH), dopamine, and second messenger agonists and inhibitors. Both PTH and dopamine inhibited phosphate transport by over 30%. The inhibitory effect of PTH was completely abolished in the presence of chelerythrine, a PKC inhibitor, but not by Rp-cAMP, a PKA inhibitor. By contrast, both chelerythrine and Rp-cAMP blocked the inhibitory effect of dopamine. Chelerythrine inhibited PTH-mediated cAMP accumulation but also blocked the inhibitory effect of 8-bromo-cAMP on phosphate transport. On the other hand, Rp-cAMP had no effect on the ability of DOG, a PKC activator, to inhibit phosphate transport. PD98059, an inhibitor of MAPK, had no effect on PTH- or dopamine-mediated inhibition of sodium-phosphate cotransport. Finally, compared with 8-bromo-cAMP, 8-pCPT-2′- O-Me-cAMP, an activator of EPAC, had no effect on phosphate transport. These results outline significant differences in the signaling pathways utilized by PTH and dopamine to inhibit renal phosphate transport. Our results also suggest that activation of MAPK is not critically involved in PTH- or dopamine-mediated inhibition of phosphate transport in mouse renal proximal tubule cells in culture.

scholarly journals Impaired Na+−K+-ATPase signaling in renal proximal tubule contributes to hyperuricemia-induced renal tubular injury

2018 ◽  
Vol 50 (3) ◽  
pp. e452-e452 ◽  
Author(s):  
Jing Xiao ◽  
Xiaoli Zhang ◽  
Chensheng Fu ◽  
Qingmei Yang ◽  
Ying Xie ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Tubular Injury ◽  
Renal Tubular

Dopamine decreases fluid reabsorption in straight portions of rabbit proximal tubule

1982 ◽  
Vol 242 (6) ◽  
pp. F634-F640 ◽  
Author(s):  
E. Bello-Reuss ◽  
Y. Higashi ◽  
Y. Kaneda
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Inhibitory Effect ◽  
Salt Transport ◽  
Rabbit Serum ◽  
Fluid Reabsorption ◽  
Receptor Sites ◽  
Direct Inhibitory Effect ◽  
Adrenergic Blockers

The effects of DA and DA blockers on fluid transport, transepithelial potential difference (PD), and Na fluxes were studied in straight portions of the rabbit proximal tubule by the technique of microperfusion in vitro. DA (10(-6) M) added to the bath (rabbit serum) produced a significant decrease in fluid reabsorption (Jv, nl.min-2.mm-1) from 0.53 +/- 0.05 to 0.19 +/- 0.06 (n = 7, P less than 0.005). PD decreased from -2.7 +/- 0.5 to -1.2 +/- 0.4 mV (P less than 0.01). Drugs active on DA receptors were used to characterize the action of dopamine. Haloperidol (10(-8) M), lisuride (1.5 X 10(-9) M), and metoclopramide (10(-7) M) did not modify Jv by themselves but prevented the action of dopamine. Agonists of DA, Epinine and A 6,7 DTN, produced smaller or shorter decreases in Jv. A 6,7 DTN was active in the presence of alpha- and beta-adrenergic blockers. The serotonin antagonist methysergide decreases Jv by itself by 15%; in its presence DA was not effective. The effect of DA was accompanied by reductions of net Na flux and unidirectional lumen-to-bath and bath-to-lumen Na fluxes by approximately 25%. It is concluded that DA exerts a direct inhibitory effect on fluid transport by the pars recta. The evidence for the existence of DA receptor sites is not conclusive. The mechanism of action is uncertain, but an impairment of transcellular salt transport can be suggested.

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