Renal organic anion secretion: evidence for dopaminergic and adrenergic regulation

1996 ◽  
Vol 271 (5) ◽  
pp. R1372-R1379 ◽  
Author(s):  
P. A. Halpin ◽  
J. L. Renfro
Keyword(s):  
Proximal Tubule ◽  
Organic Anion ◽  
Primary Cultures ◽  
Regulatory Control ◽  
Dichlorophenoxyacetic Acid ◽  
Adrenergic Stimulation ◽  
Anion Secretion ◽  
Ussing Chambers ◽  
2,4 Dichlorophenoxyacetic Acid ◽  
Organic Anion Secretion

To examine possible regulatory control of renal proximal tubule organic anion secretion, winter flounder (Pleuronectes americanus) proximal tubule primary cultures were mounted in Ussing chambers. Unidirectional fluxes of [2,4-(14)C]dichlorophenoxyacetic acid were determined under short-circuited conditions. Phorbol 12-myristate 13-acetate (1 microM) caused a significant (P < 0.01) inhibition of net 2,4-dichlorophenoxyacetic acid secretion. Preincubation with staurosporine (1 microM) blocked the phorbol 12-myristate 13-acetate-induced decrease in secretion. Neither forskolin (10 microM) nor W-7 (20 microM) had any effect on net transport. Elevation of intracellular calcium activity with either A-23187 or thapsigargin produced a slight, transient decrease in transport. Addition of dopamine (1 microM) to the peritubular side, but not the luminal side, caused a significant (P < 0.01) decrease in net secretion. Both the alpha-adrenergic agonist oxymetazoline (10 microM) and depletion of intracellular Na+ transiently, but significantly (P < 0.05), increased net transport. The data indicate that renal organic anion excretion may be regulated through dopaminergic inhibition and alpha-adrenergic stimulation of net transepithelial secretion.

Transepithelial organic anion transport by shark choroid plexus

2002 ◽  
Vol 282 (5) ◽  
pp. R1308-R1316 ◽  
Author(s):  
Alice R. A. Villalobos ◽  
David S. Miller ◽  
J. Larry Renfro
Keyword(s):  
Organic Anion ◽  
Flux Ratio ◽  
Transepithelial Transport ◽  
Dichlorophenoxyacetic Acid ◽  
Ussing Chambers ◽  
Choroid Plexuses ◽  
Epithelial Sheet ◽  
Average Flux ◽  
Dogfish Shark ◽  
2,4 Dichlorophenoxyacetic Acid

Spiny dogfish shark ( Squalus acanthias) lateral and IV choroid plexuses (CPs) are ultrastructurally similar to the corresponding tissues of rat. However, shark IV CP is proportionally larger and easily accessible. Moreover, this epithelial sheet can be halved and studied in Ussing flux chambers. We have used confocal fluorescence microscopy and radiotracer techniques to characterize transepithelial transport of the organic anions (OAs) fluorescein (FL) and 2,4-dichlorophenoxyacetic acid (2,4-D), respectively, by shark CP. Lateral and IV CP accumulated 1 μM FL, with highest levels in the underlying extracellular spaces, intermediate levels in epithelial cells, and lowest levels in the medium. 2,4-D and probenecid inhibited FL accumulation in cells and extracellular spaces, suggesting that these substrates compete for common carriers. Unidirectional absorptive [cerebrospinal fluid (CSF)-to-blood] and secretory (blood-to-CSF) fluxes of 10 μM [14C]2,4-D were measured under short-circuited conditions in IV CP mounted in Ussing chambers. 2,4-D underwent net absorption, with an average flux ratio of 7. Probenecid, 2,4,5-trichlorophenoxyacetic acid, and 5-hydroxyindolacetic acid reduced net absorption, reversibly inhibiting unidirectional absorption, with no effect on secretion. Ouabain irreversibly reduced net 2,4-D absorption and cellular and extracellular accumulation of FL, suggesting energetic coupling of OA absorption to Na+transport. Collectively, these data indicate that shark CP actively removes OAs from CSF by a process that is specific and active.

scholarly journals Organic anion secretion in polycystic kidney disease.

1997 ◽  
Vol 8 (8) ◽  
pp. 1222-1231
Author(s):  
G A Tanner ◽  
N Gretz ◽  
Y Shao ◽  
A P Evan ◽  
M Steinhausen
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Organic Anion ◽  
Left Kidney ◽  
Organic Anions ◽  
Maximal Rate ◽  
Polycystic Kidney ◽  
Fluid Accumulation ◽  
Anion Secretion ◽  
Organic Anion Secretion

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.

scholarly journals Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion

2019 ◽  
Vol 116 (32) ◽  
pp. 16105-16110 ◽  
Author(s):  
Jitske Jansen ◽  
Katja Jansen ◽  
Ellen Neven ◽  
Ruben Poesen ◽  
Amr Othman ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Gut Microbiome ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Indoxyl Sulfate ◽  
Regulation Mechanism ◽  
Uremic Toxin ◽  
Proximal Tubule Cell ◽  
Anion Secretion ◽  
Anion Transporter

Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.

scholarly journals CITOTOXICIDADE ”IN VITRO” DE CLOROFENOXIACETATO COM CÉLULAS HEPÁTICAS DE Metynnis roosevelti (PISCES, CHARACIDAE) EM CULTIVO

1999 ◽  
Vol 4 (1) ◽  
Author(s):  
LÍGIA MARIA SALVO ◽  
ROSÁRIA REGINA TESONI DE BARROS RICHARTZ ◽  
MARA ELIZA GAZINO JOINEAU ◽  
MARIA IVETTE CARBONI MALUCELLI ◽  
METRY BACILA
Keyword(s):  
Cell Viability ◽  
Microscopic Observation ◽  
Primary Cultures ◽  
Neutral Red ◽  
Dichlorophenoxyacetic Acid ◽  
Hepatic Cells ◽  
Inverted Microscope ◽  
2,4 Dichlorophenoxyacetic Acid ◽  
Direct Microscopic Observation

Células hepáticas de Metynnis roosevelti obtidas de cultivo celular primário foram submetidas a ensaios de citotoxicidade “in vitro” com os princípios ativos 2,4-D+MCPA (ácido 2,4 diclorofenoxiacético+ácido 4-cloro-2-metilfenoxiacético). Para determinação da CL50 foram utilizados dois métodos: um por meio da viabilidade celular com “vermelho neutro” e outro através da observação direta das células afetadas com microscópio invertido IM. A CL50 média das céluas hepáticas de Metynnis roosevelti em cultivo primário expostas ao 2,4D+MCPA por 24 horas, foi estabelecida entre 0,0265 g/ml e 0,0312 g/ml. Abstract “In vitro” citotoxicity of 2,4-D + MCPA (2,4-dichlorophenoxyacetic acid + 4-chloro-2- methylphenoxyacetic acid) tests were carried out with primary cultures of hepatic cells from Metynnis roosevelti (Pisces, Teleostei, Characidae). To establish the CL50 values, two different methods were used: the measurement of cell viability by means of “neutral red” and by the direct microscopic observation of the defective cells by means of an IM inverted microscope. The average CL50 value of the hepatic cells in primary cultures exposed to the chlorophenoxyacetates used, has been established between 0.0265 and 0.0312 g/ml.

Confocal microscopic analysis of fluorescein compartmentation within crab urinary bladder cells

1994 ◽  
Vol 267 (1) ◽  
pp. R16-R25 ◽  
Author(s):  
D. S. Miller ◽  
D. M. Barnes ◽  
J. B. Pritchard
Keyword(s):  
Urinary Bladder ◽  
Proximal Tubule ◽  
Organic Anion ◽  
Microscopic Analysis ◽  
Microtubule Inhibitor ◽  
Cancer Borealis ◽  
Anion Secretion ◽  
Bladder Cells

Fluorescein (FL), a fluorescent organic anion, is compartmentalized in cells of organic anion-secreting epithelia, e.g., OK cells, teleost proximal tubule, and crab (Cancer borealis) urinary bladder, a proximal tubule analogue. To further examine the processes involved, FL uptake and distribution were studied in C. borealis urinary bladder cells using epifluorescence and laser confocal microscopy combined with video-image analysis. Intracellular FL was about evenly split between diffuse and punctate compartments after in vitro or in vivo loading. Treatments that affected FL transport into cells (incubation with p-aminohippuric acid or glutarate) altered the FL content of both compartments. However, nocodazole, a microtubule inhibitor, did not affect diffuse FL but significantly reduced punctate FL. Finally, confocal analysis indicated that individual sites of punctate FL accumulation moved in the secretory direction at 0.83 micron/min. Nocodazole nearly abolished this movement and significantly reduced transepithelial organic anion secretion. Thus, in crab urinary bladder, a substantial fraction of total cellular FL is sequestered in vesicles, and these vesicles move in the secretory direction, by a microtubule-dependent process.

Protein stimulation of organic anion secretion from the liver at the sinusoidal level

1990 ◽  
Vol 183 (2) ◽  
pp. 374-375 ◽  
Author(s):  
H.M.J. Nijssen ◽  
T. Pijning ◽  
D.K.F. Meijer ◽  
G.M.M. Groothuis
Keyword(s):  
Organic Anion ◽  
Anion Secretion ◽  
Stimulation Of ◽  
Organic Anion Secretion

Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase

2005 ◽  
Vol 289 (1) ◽  
pp. F208-F216 ◽  
Author(s):  
Ryan M. Pelis ◽  
Susan L. Edwards ◽  
Stan C. Kunigelis ◽  
James B. Claiborne ◽  
J. Larry Renfro
Keyword(s):  
Metabolic Acidosis ◽  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Brush Border ◽  
Primary Cultures ◽  
Acute Effect ◽  
Renal Proximal Tubule ◽  
Ussing Chambers ◽  
Renal Tubular ◽  
Nhe Isoforms

The acute effect of metabolic acidosis on SO42− secretion by the marine teleost renal proximal tubule was examined. Metabolic acidosis was mimicked in primary cultures of winter flounder renal proximal tubule epithelium (fPTCs) mounted in Ussing chambers by reducing interstitial pH to 7.1 (normally 7.7). fPTCs with metabolic acidosis secreted SO42− at a net rate that was 40% higher than in paired isohydric controls (pH 7.7 on interstitium). The stimulation was completely blocked by the carbonic anhydrase inhibitor methazolamide (100 μM). Although Na+/H+ exchange (NHE) isoforms 1, 2, and 3 were identified in fPTCs by immunoblotting, administering EIPA (20 μM) to the interstitial and luminal bath solutions had no effect on net SO42− secretion by fPTCs with a normal interstitial pH of 7.7. However, EIPA (20 μM) blocked most of the stimulation caused by acidosis when applied to the lumen but not interstitium, demonstrating that induction of brush-border NHE activity is important. In the intact flounder, serum pH dropped 0.4 pH units (pH 7.7 to 7.3, at 2–3 h) when environmental pH was lowered from 7.8 to ∼4.3. Whereas serum [SO42−] was not altered by acidosis, renal tubular SO42− secretion rate was elevated 200%. Thus metabolic acidosis strongly stimulates renal sulfate excretion most likely by a direct effect on active renal proximal tubule SO42− secretion. This stimulation appears to be dependent on inducible brush-border NHE activity.

Sign in / Sign up

Export Citation Format

Share Document