Effects of carbonic anhydrase inhibitors on basolateral base transport of rabbit proximal straight tubule

1989 ◽  
Vol 257 (6) ◽  
pp. F947-F952 ◽  
Author(s):  
S. Sasaki ◽  
F. Marumo
Keyword(s):  
Carbonic Anhydrase ◽  
Late Phase ◽  
Carbonic Anhydrase Inhibitors ◽  
Proximal Tubule Cells ◽  
Straight Tubules ◽  
Proximal Straight Tubule ◽  
Intact Rabbit ◽  
Small Inhibition ◽  
Ph Microelectrodes

The effect of carbonic anhydrase inhibitors on basolateral base transport was examined in rabbit proximal straight tubules (S2 segment) perfused in vitro by double-barreled pH microelectrodes. Bath HCO3- reduction or Na+ removal induced an initial basolateral voltage (Vbl) depolarization followed by a late-phase depolarization. Administration of 1 mM acetazolamide (ACTZ) to the bath fluid caused a small inhibition of the initial depolarization, and a larger inhibition of the late phase depolarization. Bath HCO3- reduction decreased intracellular pH (pHi), and this pHi decrease was attenuated by ACTZ. Bath Na+ removal also decreased pHi, and this pHi decrease was completely blocked by ACTZ. However, a slow pHi decrease was observed in response to bath Na+ removal when the bath fluid contained ACTZ and the luminal fluid contained 4 mM amiloride. The addition of ACTZ or ethoxyzolamide to the bath caused a rapid Vbl hyperpolarization and pHi increase. These results demonstrate that carbonic anhydrase inhibitors inhibit basolateral Na(HCO3)n transport in intact rabbit proximal tubule cells (S2). The data suggest that at least one of the base species transported by the transporter is HCO3-, and cytosolic carbonic anhydrase is important in converting intracellular OH- to HCO3-.

Mechanism of bicarbonate exit across basolateral membrane of rabbit proximal straight tubule

1987 ◽  
Vol 252 (1) ◽  
pp. F11-F18 ◽  
Author(s):  
S. Sasaki ◽  
T. Shiigai ◽  
N. Yoshiyama ◽  
J. Takeuchi
Keyword(s):  
Negative Charge ◽  
Driving Forces ◽  
Basolateral Membrane ◽  
Disulfonic Acid ◽  
Exit Mechanism ◽  
Total Replacement ◽  
Straight Tubules ◽  
Proximal Straight Tubule ◽  
Basolateral Membrane Potential

To clarify the mechanism(s) of HCO3- (or related base) transport across the basolateral membrane, rabbit proximal straight tubules were perfused in vitro, and intracellular pH (pHi) and Na+ activity (aiNa) were measured by double-barreled ion-selective microelectrodes. Lowering bath HCO3- from 25 to 5 mM at constant PCO2 depolarized basolateral membrane potential (Vbl), and reduced pHi. Most of these changes were inhibited by adding 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) to the bath. Total replacement of bath Na+ with choline also depolarized Vbl and reduced pHi, and these changes were also inhibited by SITS. Reduction in aiNa was observed when bath HCO3- was lowered. Taken together, these findings suggest that HCO3- exists the basolateral membrane with Na+ and negative charge. Calculation of the electrochemical driving forces suggests that the stoichiometry of HCO3-/Na+ must be larger than two for maintaining HCO3- efflux. Total replacement of bath Cl- with isethionate depolarized Vbl gradually and increased pHi slightly, implying the existence of a Cl(-)-related HCO3- exit mechanism. The rate of decrease in pHi induced by lowering bath HCO3- was slightly reduced (20%) by the absence of bath Cl-. Therefore, the importance of Cl(-)-related HCO3- transport is small relative to total basolateral HCO3- exit. Accordingly, these data suggest that most of HCO3- exits the basolateral membrane through the rheogenic Na+/HCO3- cotransport mechanism with a stoichiometry of HCO3-/Na+ of more than two.

New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation

2020 ◽  
Vol 28 (15) ◽  
pp. 115586
Author(s):  
Baijayantimala Swain ◽  
Andrea Angeli ◽  
Priti Singh ◽  
Claudiu T. Supuran ◽  
Mohammed Arifuddin
Keyword(s):  
Carbonic Anhydrase ◽  
Biological Evaluation ◽  
Carbonic Anhydrase Inhibitors

Discovery of potent anti-convulsant carbonic anhydrase inhibitors: Design, synthesis, in vitro and in vivo appraisal

2018 ◽  
Vol 156 ◽  
pp. 430-443 ◽  
Author(s):  
Chandra Bhushan Mishra ◽  
Shikha Kumari ◽  
Andrea Angeli ◽  
Silvia Bua ◽  
Martina Buonanno ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Inhibitors ◽  
Design Synthesis

scholarly journals Maturation of rabbit proximal straight tubule chloride/base exchange

1998 ◽  
Vol 274 (5) ◽  
pp. F883-F888 ◽  
Author(s):  
Mehul Shah ◽  
Raymond Quigley ◽  
Michel Baum
Keyword(s):  
Adult Rabbit ◽  
Albumin Solution ◽  
Nacl Transport ◽  
Base Exchange ◽  
Straight Tubule ◽  
Volume Absorption ◽  
Straight Tubules ◽  
Proximal Straight Tubule ◽  
Proximal Tubular

The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serumlike albumin solution, the rate of volume absorption ( J V) was 0.54 ± 0.10 and 0.12 ± 0.05 nl ⋅ mm−1 ⋅ min−1in adults and neonates, respectively ( P < 0.05). With the addition of 10−5 M bath ouabain, J Vdecreased to 0.27 ± 0.07 and −0.03 ± 0.04 nl ⋅ mm−1 ⋅ min−1in adult and neonatal tubules, respectively ( P < 0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The effect of luminal sodium and chloride removal on intracellular pH was used to assess the relative rates of Na+/H+and Cl−/base exchange. The rates of Na+/H+and Cl−/base exchange were approximately fivefold less in neonatal proximal straight tubules than adult tubules. In both neonatal and adult proximal straight tubules, the rate of Cl−/base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, consistent with Cl−/OH−exchange. These data demonstrate an increase in proximal straight tubule NaCl transport during postnatal renal development.

Urinary acidification: CO2 transport by the rabbit proximal straight tubule

1977 ◽  
Vol 232 (1) ◽  
pp. F20-F25 ◽  
Author(s):  
D. G. Warnock ◽  
M. B. Burg
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Functional Heterogeneity ◽  
High Permeability ◽  
Straight Tubule ◽  
Urinary Acidification ◽  
Straight Tubules ◽  
Proximal Straight Tubule ◽  
Tubule Fluid

Proximal straight tubules from rabbit kidneys were perfused in vitro in order to study transport of bicarbonate. Total CO2 content was measured in perfused and collected tubule fluid, using microcalorimetry. When the initial perfusate and bath contained 25 mM bicarbonate, the concentration of total CO2 decreased in the collected tubule fluid, indicating net reabsorption of bicarbonate. When the initial perfusate contained no bicarbonate and the bath contained 25 mM bicarbonate, total CO2 appeared in the collected tubule fluid. The rate at which total CO2 appeared in the tubule fluid was rapid, indicating a high permeability. Proximal straight tubules from superficial and juxtamedullary nephrons were compared and found to differ in permeability to CO2 and in transport rate. This functional heterogeneity may affect urinary acidification when there is redistribution of renal blood flow.

Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids

2011 ◽  
Vol 28 (2) ◽  
pp. 283-288 ◽  
Author(s):  
Derya Ekinci ◽  
Lutfi Karagoz ◽  
Deniz Ekinci ◽  
Murat Senturk ◽  
Claudiu T. Supuran
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Inhibitors ◽  
In Vitro Inhibition

Magnesium transport in the proximal straight tubule of the rabbit

1984 ◽  
Vol 246 (5) ◽  
pp. F544-F550 ◽  
Author(s):  
G. A. Quamme ◽  
C. M. Smith
Keyword(s):  
Magnesium Concentration ◽  
Concentration Gradients ◽  
Magnesium Transport ◽  
Dietary Magnesium ◽  
Straight Tubules ◽  
Proximal Straight Tubule ◽  
Intact Kidney ◽  
Tubule Fluid ◽  
Fractional Absorption

Magnesium transport was evaluated in proximal straight tubules of rabbits by in vitro perfusion. Magnesium transport from lumen to bath was less than the fractional absorption rates of sodium and calcium. Accordingly, the tubule fluid magnesium concentration increased with water absorption. Magnesium transport in proximal straight tubules obtained from rabbits maintained on high dietary magnesium intake was not different from normal animals, which suggests little, if any, change in tubular function. There were no discernible differences in magnesium fluxes between superficial and juxta-medullary proximal straight tubules. To assess bath-to-lumen magnesium flux, tubules were perfused with solutions containing zero magnesium concentration. Magnesium movement from the bath to lumen was small and dependent on the transepithelial magnesium concentration gradient. This magnesium influx may be sufficient to account for net magnesium entry provided the appropriate concentration gradients from interstitium to lumen are available in the intact kidney.

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