Regulation of plasma choline by the renal tubule: bidirectional transport of choline

Acara, M; Rennick, Barbara R.

doi:10.1152/ajplegacy.1973.225.5.1123

Cited by 57 publications

(22 citation statements)

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“…The results of this study suggest that appre- (1). This interpretation of our data is consistent with recent evidence indicating that gentamicin is handled primarily by reabsorption.…”

supporting

confidence: 92%

Effect of N ′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats

Jerauld¹,

Silverblatt²

1978

Antimicrob Agents Chemother

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N'-methylnicotinamide, a substrate of the organic base transport system, reduced renal accumulation of ["4C]gentamicin in rats by 15% and increased clear-ance by 25%, suggesting that gentamicin is not secreted by this mechanism.High concentrations of gentamicin persist in the renal cortex of humans and experimental animals long after the antibiotic is discontinued (4, 5). In rats and probably in humans, this accumulation is accompanied by injury of the proximal tubule epithelium (3, 5). The mechanism whereby gentamicin is transported into the proximal cell is not known. Like other substances handled by the proximal tubule, gentamicin could enter the cell either from the glomerular filtrate or across the contraluminal surface. Because gentamicin has several amine groups, Whelton and Walker suggested that the drug might be carried into the cell by the organic base transport system (8). This mechanism actively transports certain organic cations, such as N'-methylnicotinamide (NMN), across the contraluminal membrane and into the urine (7). To determine whether a significant proportion of gentamicin enters the proximal tubular cell by means of the organic base transport system, we studied the effect of NMN on renal clearance and tissue accumulation of ['4C] sacrificed and nephrectomized 22 h after completion of the infusion. The cortex was separated from medulla, and the two portions were minced and homogenized in 0.25 M sucrose solution. All samples (plasma, urine, and renal homogenate) were prepared for liquid scintillation counting. Gentamicin clearances for each 20-min interval were calculated by the standard formula. Renal gentamicin accumulation in each animal was expressed as the total amount of gentamicin in the renal tissue in both kidneys and as the percentage of the administered dose recovered in both kidneys.During the sustaining infusion, plasma gentamicin levels did not vary by more than 15% in each animal, indicating that a steady state had been achieved. There was no significant difference between the mean plasma gentamicin levels for NMN-treated animals and control animals, 7.17 + 0.29 and 7.38 ± 0.32 /,g/ml, respectively (Table 1). The mean gentamicin clearance for the NMN-treated animals was 7.78 + 0.32 ml/min per kg of animal weight, which was significantly higher than the gentamicin clearance in the controls, 5.95 + 1.30 ml/min per kg of body weight (P < 0.01).NMN had a less profound, but nonetheless significant effect on renal accumulation of gentamicin (Table 1). The average amount of gentamicin in the renal tissue was 94.1 + 6.1 ,g for the NMN-treated group and 111.1 + 4.9 ,ug for controls (P < 0.05). A mean of 5.2 ± 0.1% of the administered gentamicin dose was recovered in the renal tissue of NMN-treated animals, compared to 6.4 ± 0.7% in controls (P < 0.01). The amount of label in the papilla and inner medulla was undetectable.The results of this study suggest that appre-

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“…The results of this study suggest that appre- (1). This interpretation of our data is consistent with recent evidence indicating that gentamicin is handled primarily by reabsorption.…”

supporting

confidence: 92%

Effect of N ′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats

Jerauld¹,

Silverblatt²

1978

Antimicrob Agents Chemother

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“…Choline enters renal cells rapidly (Acara and Rennick, 1973;Gardiner and Gwee, 1974;Toback et al, 1974), and probably by active transport (Sung and Johnstone, 1965). From previous studies it is known that the radioactive label on [ 14 C]methyl-labeled choline does not transfer to other cell components (Plagemann, 1968), and that free choline does not exchange with choline in phos- phatidylcholine (Plagemann, 1971;Wheldrake, 1972).…”

Section: Discussionmentioning

confidence: 99%

Choline uptake into renal phospholipids following renal ischemia in rats.

Siegel¹,

Lowenstein²,

Levinsky³

1979

Circulation Research

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SUMMARY Renal phospholipid metabolism was studied after ischemia was induced by occlusion of the left renal artery in the rat. There was no change in the rate of cellular ["C]choline uptake after 25 or 80 minutes of ischemia. However, [ u C]choline incorporation into phospholipid was two to three times greater in slices from the ischemic kidney than in slices from the contralateral control kidney. The increase occurred after 25 minutes of ischemia plus 15 minutes of reflow, and after 60 minutes of ischemia with or without reflow. When [ u C]choline was injected into rats after a 60-minute period of renal ischemia, the rate of incorporation into phospholipid in the ischemic kidney was almost twice that of the control kidney. These results were similar to those of the in vitro experiments. Since virtually all of the cellular phospholipids of the kidney are present in cellular membranes, renal ischemia affects membrane metabolism. The mean distribution ratio of a-aminoisobutyric acid in slices of kidneys ischemic for 60 minutes was similar to that of control slices DAMAGE to cell membranes is a prominent feature of renal ischemia. In rats, after occlusion of the renal artery for periods up to 1 hour, the damage is especially evident in the proximal tubular cells, which become denuded of brush border membranes (Reimer and Jennings, 1971a;Reimer et al., 1972;Venkatachalam et al., 1978). If the ischemic period is short, the membranes regenerate; with longer periods of ischemia, cellular necrosis ensues. Phospholipids are the basic structural component of cellular membranes. We therefore investigated membrane metabolism in renal ischemia by determining the rate of incorporation of [ u C]choline into phospholipid of ischemic rat kidneys. We also determined the transport of a-aminoisobutyric acid (AIB) in the kidneys, since the membrane damage might be expected to affect the membrane transport of metabolites. MethodsMale Sprague-Dawley rats, weighing 250-350 g (Charles River Breeding Laboratories, Inc.) and fed rat chow, were used. They were anesthetized with Inactin, 100 mg/kg body weight, placed on a heated board to maintain body temperature at 37°C, and continuously infused with heparinized saline (6 U aqueous heparin/ml 0.85% saline) into the left jugular vein at 28 fil/min. Tubing in the right femoral artery was attached to a Hewlett-Packard pressure transducer and recorder for continuous blood pressure measurements. Through a left flank incision, the left kidney and ureter were freed from surrounding fat, and the kidney was covered with cotton immersed in mineral oil at 37°C. The left renal artery was totally occluded with a modified aluminum Blalock clamp for periods of from 25 minutes to 3 hours and then released. Adequacy of clamping was assessed by blanching of the kidney and by the absence of a vascular flush after a venous injection of 50 jd of 5% lissamine green midway during the ischemic period. Adequacy of reflow after removal of the clamp was assessed by the return of normal color and by a vascular flush ...

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“…The kidney choline concentration was significantly decreased by HC-3 (40%) and TPHC-3 (30%). This might be due to the hemicholinium inhibiting the tubular reabsorption of choline in the glomerular filtrate as shown by Vander (1962) and Acara & Rennick (1973). The intracellular choline concentration can then be expected to fall, since the choline will continue to undergo metabolism without being replaced.…”

Section: Effect Of Hemicholinium-3 On Continuous Infusions Of Cholinementioning

confidence: 99%

Effect of Two Hemicholiniums on the Disposition and Distribution of Endogenous Free Choline in Anaesthetized Rabbits

Gardiner

Gwee

1977

British J Pharmacology

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1 The effects of hemicholinium no. 3 (HC‐3) and its p‐terphenyl analogue (TPHC‐3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay. 2 The respiration of animals given 0.35 μmol/kg of HC‐3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC‐3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC‐3 (1.4 μmol/kg) or TPHC‐3 (0.7 μmol/kg) developed respiratory difficulty about 1 h after the second injection. 3 The respiratory distress was accompanied by a 2 to 15‐fold rise in plasma choline concentration. This rise has been attributed to hypoxia. 4 In experiments in which choline has been infused it was observed that HC‐3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC‐3 nor TPHC‐3 produced changes in plasma choline concentrations unless the respiration was depressed. 5 Either HC‐3 or TPHC‐3 (both at 0.35 μmol/kg) significantly (P < 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC‐3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.

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Regulation of plasma choline by the renal tubule: bidirectional transport of choline

Cited by 57 publications

References 0 publications

Effect of N ′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats

Effect of N ′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats

Choline uptake into renal phospholipids following renal ischemia in rats.

Effect of Two Hemicholiniums on the Disposition and Distribution of Endogenous Free Choline in Anaesthetized Rabbits

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