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N Hagiwara

Publications and source records attributed to N Hagiwara.

At least 73 records · Page 4Linked to original sources

Effects of insulin and tyrosine kinase inhibitor on ion transport in the alveolar cell of the fetal lung.

We studied the effect of insulin and lavendustin-A (a tyrosine kinase inhibitor) on the short-circuit current (ISC) of primary cultures of fetal distal rat lung epithelium (FDLE). Insulin (2 microM) on the basolateral side of the monolayer increased ISC from 5.76 +/- 0.83 microA/cm2 (SEM, n = 7) to 7.23 +/- 1.00 microA/cm2 (p less than 0.01) under control conditions, and from 1.00 +/- 0.31 microA/cm1 to 1.53 +/- 0.34 microA/cm2 (p less than 0.05, n = 4) when amiloride (10 microM) was present on the apical side of the monolayer. Thus insulin increased both the amiloride-sensitive and insensitive ISC with the insulin-induced increase in ISC in the absence of amiloride (1.47 +/- 0.22 microA/cm2, n = 7) being significantly larger than that in the presence of 10 microM amiloride (0.53 +/- 0.14 microA/cm2, n = 4; p less than 0.025). Insulin's effect reached steady state in 1 hr. Lavendustin-A (10 microM), a tyrosine kinase inhibitor, applied to the apical side of the monolayer attenuated but did not completely block insulin's ability to increase in ISC; i.e., insulin increased ISC in lavendustin-A treated monolayers (0.63 +/- 0.09 microA/cm2, n = 5; p less than 0.0025) but the increase was significantly smaller than that without the pretreatment of lavendustin-A (p less than 0.05). In the presence of amiloride (10 microM) and lavendustin-A (10 microM) insulin was no longer able to increase ISC (change in ISC = 0.04 +/- 0.03 microA/cm2, n = 6), suggesting that lavendustin-A had blocked the insulin's effect on the amiloride-insensitive ISC. Lavendustin-A (10 microM) had no significant effect on the basal ISC in control and amiloride treated monolayers. Our studies demonstrate that insulin increases amiloride-insensitive ISC in FDLE via lavendustin-A sensitive tyrosine kinase and that insulin's action on the amiloride-sensitive ISC of FDLE is mediated through a lavendustin-A insensitive (and presumably tyrosine kinase-independent) pathway.

Amiloride↗

Background current in sino-atrial node cells of the rabbit heart.

1. The Ca2+ current, K+ current, hyperpolarization-activated current, Na(+)-K+ pump current and the Na(+)-Ca2+ exchange current were all blocked by appropriate blockers and the remaining time-independent currents were investigated in single pacemaker cells of the rabbit sino-atrial node using the whole-cell patch clamp technique. 2. Exchanging the bathing solution from Tris-hydroxymethyl-aminomethane hydrochloride (Tris) Na+ free to 150 mM-Na+ induced an inward current and the slope conductance of the current-voltage relationship increased from 0.45 +/- 0.18 to 0.87 +/- 0.33 nS (n = 71) at -50 mV. The remaining conductance in Tris Na(+)-free solution was essentially the same when Tris was substituted with tetraethylammonium (TEA) or N-methyl-D-glucamine (NMG). The current density of the Na(+)-dependent inward current obtained by subtracting the current in Tris Na(+)-free from that in 150 mM-Na+ solution was 0.73 +/- 0.21 pA/pF (n = 71) at -50 mV. We called this current the Na(+)-dependent background current. 3. The membrane conductance was reduced by lowering the temperature of the external solution from 36 to 23 degrees C. In Tris Na(+)-free solution, the temperature-sensitive component was outward at all potentials, whereas it showed a reversal potential at around -20 mV in 150 mM-Na+ solution. This reversal potential was interpreted as a sum of the Cs+ efflux and Na+ influx, by comparing the Na(+)-dependent inward currents obtained at 36 degrees C and those at 23 degrees C. 4. Divalent cations (2 mM-Ni2+, 1 mM-Ba2+ or 2 mM-Ca2+) reduced only the outward current in the Tris Na(+)-free solution, while in the 150 mM-Na+ solution, they reduced both the inward and outward components of the current which had a reversal potential of around -10 mV. 5. Amiloride depressed the membrane conductance in 150 mM-Na+, Cs+ or Rb+ external solution, though only at negative membrane potentials, which suggests amiloride has a voltage-dependent effect on the background current. 6. Removal of Cl- from the external solution or the addition of a Cl- channel blocker (4,4'-dinitrostilbene-2,2'-disulphonic acid disodium salt, DNDS) failed to affect the membrane conductance. 7. When the monovalent cation-dependent inward current was measured by subtracting the current in the Tris solution from those recorded in the various monovalent cation solutions, the current amplitude decreased in the order: Rb+ greater than K+ greater than Cs+ greater than Na+ greater than Li+, which suggests a poor cation selectivity of this current system.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗

Stretch-activated anion currents of rabbit cardiac myocytes.

1. Stretch-activated anion currents were studied in sino-atrial and atrial cells using the whole-cell patch clamp technique. With continuous application of positive pressure (5-15 cmH2O) through the patch clamp electrode, the cell was inflated and the membrane conductance was increased. 2. Voltage clamp steps revealed that the stretch-activated currents had time-independent characteristics. The increase in membrane conductance was reversible on subsequent application of negative pressure to the electrode. 3. The reversal potential of the stretch-activated currents was shifted by 60 mV for a 10-fold change in intracellular Cl- concentration, while it was unaffected by replacement of Na+ in the extracellular solution by N-methyl-D-glucamine. Cell superfusion with Cl(-)-deficient solution (10 mM Cl-) reduced the amplitude of outward current. These findings indicate that the stretch-activated conductance is Cl- selective. 4. The sequence of anion permeability through the stretch-activated conductance was determined to be I-(1.7) > NO3-(1.5) > Br-(1.2) > Cl-(1.0) > and F-(0.6). SCN- appeared to be more permeant than I-. 5. The stretch-activated conductance was reduced by the Cl- channel blockers, 4,4'-dinitrostilbene-2,2'-disulphonic acid disodium salt, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid or anthracene-9-carboxylate (9-AC). Administration of furosemide or bumetanide had no effect. 6. The stretch-activated Cl- current was recorded even though intracellular Ca2+ ions were chelated by including 10 mM EGTA in the pipette solution. Neither the specific peptide inhibitor of cyclic AMP-dependent protein kinase (50 microM), nor the non-selective blocker of protein kinases, H-7 (20 microM), was effective in reducing the stretch-activated Cl- current, suggesting that the stretch-activated Cl- current is a novel type of cardiac Cl- current, which shows a different modulatory mechanism from that of other cardiac Cl- currents.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6).

Using the patch-clamp technique, we studied the effect of insulin on an amiloride-blockable Na channel in the apical membrane of a distal nephron cell line (A6) cultured on permeable collagen films for 10-14 days. NPo (N, number of channels per patch membrane; Po, average value of open probability of individual channels in the patch) under baseline conditions was 0.88 +/- 0.12 (SE)(n = 17). After making cell-attached patches on the apical membrane which contained Na channels, insulin (1 mU/ml) was applied to the serosal bath. While maintaining the cell-attached patch, NPo significantly increased to 1.48 +/- 0.19 (n = 17; P less than 0.001) after 5-10 min of insulin application. The open probability of Na channels was 0.39 +/- 0.01 (n = 38) under baseline condition, and increased to 0.66 +/- 0.03 (n = 38, P less than 0.001) after addition of insulin. The baseline single-channel conductance was 4pS, and neither the single-channel conductance nor the current-voltage relationship was significantly changed by insulin. These results indicate that insulin increases Na absorption in the distal nephron by increasing the open probability of the amiloride-blockable Na channel.

Amiloride↗

[Pharmacokinetic, bacteriological and clinical studies on meropenem in children].

Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30-minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction.

The effect of green tea polyphenol fraction (GTP) on azoxymethane(AOM)-induced colon carcinogenesis was investigated in male Fischer rats. The rats were given AOM (7.4 mg/kg body weight) s.c. once a week for 10 weeks. A week after the treatment, they were divided into three groups: AOM-control (26 rats), AOM-GTP1 (26 rats) and AOM-GTP2 (25 rats). AOM-GTP1 and AOM-GTP2 groups respectively received 0.01 and 0.1% GTP in drinking water from week 11 to 26. AOM-control group received tap water throughout this experiment. Autopsy on week 26 showed that tumor incidence and average numbers of tumors per rat in the AOM-GTP1 and AOM-GTP2 groups were significantly lower than those of the AOM-control group: 38.1% and 47.6% versus 77.3%; 0.6 and 0.7 versus 1.5. Thus, it was concluded that GTP inhibited the development of AOM-induced colon carcinogenesis. The inhibition by GTP did not show significant dose dependence.

Animals↗

Ion-selective microelectrodes to study proton and bicarbonate transport in the renal epithelium.

We have developed several kinds of ISM, and obtained valuable information. The method presented provides (1) the data in situ, and (2) simultaneous data of the membrane potential and the selected ionic activities. Both of these give the driving forces for ion fluxes across the individual membrane border. They provide not only the knowledge of ionic status in minute spaces but also the relationship between different ionic species which are measured simultaneously in the living cell. Further information could also be available by employing this ISM method in combination with the relevant techniques, such as patch-clamp and fluorescent dye techniques.

Animals↗

Relationship between cytosolic activities of calcium and pH in frog proximal tubules.

To examine the effect of acid-base changes on the cytosolic calcium activity, (Ca)i, we used ion-selective microelectrodes in doubly perfused preparations of bullfrog kidney proximal tubule. For analyzing the time course of changes in (Ca)i and cytosolic pH (pHi) in response to peritubular acid or alkali perfusion and high K+, low Na+, or low Ca2+ perfusion single-barreled PVC-resin Ca2(+)-selective microelectrodes and double-barreled pH-sensitive microelectrodes were inserted into the cells. Control values (mean +/- S.E., number of observations) of (Ca)i and pHi averaged 17.2 +/- 1.0 nM (n = 25) and 7.39 +/- 0.01 (n = 25), respectively. Peritubular perfusion with a low pH perfusate (low HCO3-, pH 6.7) was found to reduce (Ca)i to about 4 nM in association with a moderate degree of cell acidification (to pH 7.09) and depolarization of the peritubular membrane potential (control -60 mV to experimental approximately -40 mV). Further, peritubular alkalinization (high HCO3- 30 mM, pH 8.0) induced a transient elevation of (Ca)i and hyperpolarization. In contrast, the peritubular perfusion of high K+ solution induced a rise of (Ca)i and pHi with membrane depolarization, while low Na+ perfusion decreased (Ca)i and pHi. These results support the view that 1) the experimentally induced changes in the membrane potential may be ascribed in large part of alterations of pH-sensitive conductance across the peritubular membrane, and 2) the cell pH and extracellular Ca2+ affect the cytosolic Ca2+ of the proximal tubule.

Acid-Base Equilibrium↗

Effects of dopamine on the transport of Na, H, and Ca in the bullfrog proximal tubule.

UNLABELLED: To study effects of dopamine (DA, 10(-6) M) on ion transport processes in proximal tubular cells, we used Na(+)-, H(+)-, and Ca2(+)-selective microelectrodes in doubly-perfused bullfrog kidneys. The peritubular membrane potential difference (EM) and cytosolic Na+, Ca2+, and H+ activities ((Na)i, (Ca)i, and pHi) were measured continuously after peritubular administration of DA or dibutyryl-cyclic AMP (db-cAMP, 10(-4) M). Results obtained are as follows. 1) DA induced a decrease of (Na)i by 4.2 mM, but during the luminal perfusion of 0.5 mM Na+ solution, DA decreased (Na)i only by 1.4 mM. 2) DA produced a delayed fall of (Ca)i by 8 nM. 3) DA produced hyperpolarization of EM by 5-7 mV. 4) Peritubular perfusion with high K+ (35 mM) solution produced about 30 mV depolarization of EM. DA added to high K+ perfusate induced 38 mV depolarization. 5) DA increased pHi by 0.07. 6) DA produced almost the same changes in (Na)i, (Ca)i, EM, and pHi as those induced by db-cAMP. 7) Effects of DA on EM and (Na)i were inhibited by dopamine1 (DA1) antagonist. CONCLUSIONS: Effects of DA on ion transport in the proximal tubular cells are mediated by the adenylate-cyclase-cAMP system. The activation of this system induces 1) suppression of Na+ entry step across the luminal membrane, 2) an increase of K+ permeability in the peritubular membrane, 3) cytosolic alkalinization with vesicular accumulation of H+ by enhancing H+ pump, and 4) a decrease of (Ca)i possibly by restricting Ca2+ entry across the luminal membrane and activating Ca2+ pump in the peritubular membrane or subcellular organelles.

Adenylyl Cyclases↗

Intracellular calcium measurements with PVC-resin Ca-selective microelectrodes in frog proximal tubules and sartorius muscle fibers.

To measure ion activity of intracellular calcium, (Ca)i, we manufactured a Ca2(+)-selective microelectrode based on a neutral carrier, ETH-1001, with or without polyvinylchloride column (PVC-resin). Before and after cell impalements (n = 7), PVC-resin Ca2(+)-selective microelectrodes exhibited Nernstian slopes in the range of p(Ca) from 3 to 7 (the mean slope constant: 29.1 and 29.4 mV/p(Ca), respectively) and sub-Nernstian slopes between p(Ca) = 7 and 8 (21.6 and 21.1 mV/p(Ca]. Individual detection limits of PVC-resin microelectrodes averaged p(Ca) = 8.5 before and 8.3 after cell impalements. In contrast, the non-PVC-resin microelectrode exhibited a poor response between p(Ca) = 7 and 8 especially after cell impalements. Normal values obtained with the PVC-resin microelectrode for (Ca)i of proximal tubule cells and resting sartorius muscle fibers in the bullfrog averaged 18 +/- 2 (n = 10) and 12 +/- 2 (n = 7) nM (mean +/- S.E., number of observations), respectively. We conclude that 1) the PVC-resin microelectrode is a useful tool for measuring intracellular ion activities, and 2) the values of intracellular Ca2+ activity of the proximal tubule and skeletal muscle fibers measured with this microelectrode are in a lower range among the various values reported before with the other methods.

Animals↗

Modulation by intracellular Ca2+ of the hyperpolarization-activated inward current in rabbit single sino-atrial node cells.

1. The sensitivity to internal Ca2+ of the hyperpolarization-activated inward current (Ih or If) in rabbit single sino-atrial node cells was investigated by the whole-cell voltage-clamp method. 2. When the patch pipette contained an internal solution of pCa 10, the amplitude of If decreased by 74.8 +/- 3.3% in 10 min (n = 7) after rupture of the patch membrane. When the pipette contained an internal solution of pCa 7, If increased by 43.7 +/- 8.7% within 10 min (n = 5). 3. Increase of If by the higher Ca2+ internal solution was confirmed in the same cell using the cell dialysis method. Both If and its tail current were increased at every membrane potential. The amplitude of If increased most markedly between pCa 8 and 7. 4. The reversal potential and kinetics of If were unaffected by the internal Ca2+ concentration. Increase of If by the high internal Ca2+ concentration was sensitively blocked by Cs+. These findings confirm that the increased current is indeed If and not a newly activated If-like current due to elevation of internal Ca2+. 5. The activation curve of If shifted approximately 13 mV in a positive direction by elevating Ca2+ from pCa 10 to 7 (n = 21), indicating that the voltage dependence of If was modulated by internal Ca2+. 6. beta-Agonists also modulated If, but the underlying mechanisms of their effects on If differed from those of the internal Ca2+. The former affected the If kinetics rather than its amplitude, whereas the latter acted on the If conductance rather than on its kinetics. 7. The increase in If by the internal Ca2+ was unaffected by protein kinase inhibitor or calmodulin inhibitor, suggesting that the internal Ca2+ directly modulates If. 8. When the patch pipette contained pCa 7 internal solution, the maximum diastolic potential shifted towards a positive potential but the heart rate remained almost constant.

Action Potentials↗

Effects of norepinephrine on the proximal tubular cells in perfused bullfrog kidney.

UNLABELLED: To study effects of norepinephrine (NE) on sodium and hydrogen ion transport, we used H(+)-, Ca2(+)-, or Na(+)-selective microelectrode and split-oil droplet techniques in doubly-perfused bullfrog proximal tubules. Peritubular membrane potential difference (EM), intracellular activities of Na+ ((Na)i) and Ca2+ ((Ca)i), and pH of the cytosol (pHi) and the lumen (pHTF) were monitored continuously during peritubular administration of NE (10(-6)-10(-7) M), phenylephrine (PHE, 10(-7) M), or dibutyryl cyclic AMP (db-cAMP, 10(-4) M). RESULTS: (1) The peritubular application of NE produced: a) an enhancement of proximal fluid reabsorption, b) a transient fall of pHTF by about 0.2, c) a gradual hyperpolarization of EM and a slight decrease of (Na)i with oscillation, d) a mild cell acidification by about 0.05 pH, and e) an increase of (Ca)i. (2) The peritubular perfusion of PHE (alpha 1-agonist) caused: a) a transient fall of pHTF by about 0.3, b) a transient depolarization of EM and an increase of (Na)i, followed by sustained hyperpolarization of EM and a decrease of (Na)i, c) cytosolic acidification by about 0.1 pH, and d) a slight decrease of (Ca)i, followed by a sustained increase of (Ca)i. (3) The peritubular application of db-cAMP produced: a) a reduction of proximal fluid reabsorption, b) a transient elevation of pHTF by about 0.15, c) a hyperpolarization of EM with a gradual decrease of (Na)i, d) cytosolic alkalinization by about 0.15 pH, and e) biphasic change of (Ca)i: i.e., a slight increase of (Ca)i followed by a sustained decrease of (Ca)i.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells.

1. Two types of calcium currents, the transient type and long-lasting type, were examined by both whole-cell and cell-attached patch-clamp modes in single isolated sino-atrial node cells of the rabbit. 2. In the whole-cell clamp mode, in response to a depolarizing pulse to -40 mV from a holding potential of -80 mV, a transient type calcium current with an amplitude of 2.1 +/- 0.7 pA/pF (mean +/- S.D.; n = 15) was recorded. The threshold potential was approximately -50 mV. 3. Nickel (40 microM) and tetramethrin (0.1 microM) blocked the transient type calcium current without appreciable effects on the long-lasting type. Nifedipine and D600 blocked the long-lasting type, but did not affect the transient type. Cadmium (20 microM) and cobalt (2 mM) inhibited both types of calcium currents equally. 4. Both types of calcium currents showed an increased amplitude with increasing extracellular calcium concentration. The values of the Michaelis constant, Km, were 0.95 mM for the transient type and 3.92 mM for the long-lasting type, indicating that these types represent two different classes of channels. 5. In the cell-attached patch-clamp mode, the single-channel conductance of the transient type calcium current was 8.5 pS, by using 100 mM-BaCl2 in the pipette, whereas that of the long-lasting type was 16.0 pS, under the same conditions. Each of these values was similar to those found in other cells, respectively. 6. In the whole-cell clamp mode, the transient type current began to inactivate at -70 mV and was fully inactivated at -40 mV. The steady-state inactivation curve of the transient type current was approximately 50 mV negative to that of the long-lasting type. The overlap of the membrane potential between the activation and inactivation curves was small. The time constant of the inactivation shortened from 20 to 5 ms as the potential became progressively positive over the range from -80 to +30 mV. 7. Isoprenaline (1 microM) increased the amplitude of the long-lasting type Ca2+ current, but was not effective on the transient type, suggesting that the long-lasting type calcium current may be responsible for the positive chronotropic effect of isoprenaline. 8. While recording spontaneous electrical activity of the cell, application of 40 microM-nickel induced bradycardia and this effect was enhanced when the membrane was constantly hyperpolarized.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

A case of giant mediastinal leiomyoma with long-term survival.

A 67-year-old female was emergently admitted to our hospital because of severe dyspnea with cyanosis. One month before admission, she consulted a doctor and chest x-ray disclosed a huge tumor shadow occupying most of the left hemithorax. At that time, she did not complain of any particular symptoms except slight cough. Twelve days after admission, the patient lost consciousness and an emergency operation was performed. The tumor showed severe adhesion to the aorta and the lower lobe of the left lung, but not to the esophagus. After the operation, mechanical ventilation was necessary for 13 days to recover pulmonary function. Histological diagnosis was made as leiomyoma, which is rarely seen in the mediastinal region. At present, the patient survived 10 years without any symptom of recurrence. In this paper, the authors report a case of mediastinal leiomyoma which received an emergency operation and attained long term survival. Twelve similar cases reported in the past were also reviewed.

Aged↗

The effect of ouabain, insulin, and cyclic AMP on the acidification of luminal fluid in the proximal tubule of bullfrog kidney.

A transient urinary acidification was induced in the bullfrog proximal tubule by the peritubular administration of ouabain (10(-4) M). Insulin (200 mIU/ml) provoked a prolonged decrease of tubular fluid pH (TFpH), whereas dibutyryl cyclic AMP (10(-4) M) produced a transient increase of TFpH. The above data support the view that the urinary acidification in the proximal tubule is not explained by a simple mechanism, such as Na+/H+ exchange.

Amiloride↗

The effect of cAMP on ion transport in the proximal tubular cells in bullfrog kidney.

UNLABELLED: Using a direct cellular micropuncture technique with double-barreled ion-selective microelectrodes, we investigated the effect of dibutyryl-cyclic AMP (db-cAMP) on the membrane potential and the transport of Na+, K+, and H+ in doubly-perfused bullfrog proximal tubules. The peritubular membrane potential difference (EM) and the intracellular K+, Na+ activities ((K)i, (Na)i) or intracellular and luminal pH were monitored continuously after peritubular administration of db-cAMP (10(-3)-10(-4)M). RESULTS: 1) db-cAMP hyperpolarized the EM by 8.0 mV with an increase of (K)i by 4.8 mEq/l; 2) the peritubular administration of high K+ (13.5 and 50 mM) solutions depolarized the EM by 11.5 and 41.5 mV, respectively. The high K+ perfusate with db-cAMP produced a depolarization to the same level as that in simple high K+ perfusion without db-cAMP; 3) db-cAMP transiently blocked the luminal acidification concomitantly with a cellular alkalinization by about 0.1 pH; and 4) db-cAMP caused a decrease of (Na)i by 5.0 mEq/l. CONCLUSIONS: 1) cAMP causes an increase of K+ permeability in the peritubular membrane; 2) cAMP induces a cytosol alkalosis by enhancing incorporation of H+ into the subcellular vesicles, thus favoring the activation of Na+/K+ pump; and 3) cAMP, in effect, suppresses the Na+/H+ exchange mechanism in the luminal membrane and transiently blocks the proximal urinary acidification.

Animals↗