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Effect of fetal exposure to gentamicin on phosphate transport in young rat kidney
M Lelievre-Pegorier1, S Euzet, C Merlet-Benichou
1Unité de Recherches sur le Développement Normal et Pathologique des Fonctions Epithéliales, Institut National de la Santé et de la Recherche Médicale Unité 319, Université Paris 7, France.
Insights
Maternal gentamicin exposure in rats impairs renal phosphate reabsorption in offspring. This occurs because gentamicin alters the maturation of the sodium-phosphate cotransporter
Area of Science:
- Nephrology
- Developmental Biology
- Pharmacology
Background:
- Renal phosphate (Pi) transport capacity typically increases during the third postnatal week in rats due to enhanced carrier system affinity.
- Rat pups born to mothers treated with gentamicin exhibit impaired tubular Pi reabsorption during this critical developmental period.
Purpose of the Study:
- To investigate if in utero gentamicin exposure selectively disrupts the postnatal maturation of the renal phosphate (Pi) carrier system's affinity.
Main Methods:
- Studied sodium-phosphate (Na-Pi) cotransport and glucose transport in proximal tubule brush-border membrane (BBM) vesicles from control and gentamicin-exposed rats.
- Assessed maximal rate of uptake (Vmax) and Michaelis constant (Km) for Na-Pi cotransport.
- Analyzed BBM alkaline phosphatase activity and membrane composition (phospholipids, cholesterol).
Main Results:
- Gentamicin-exposed rats showed a significantly lower Vmax for Na-Pi cotransport compared to controls (536 vs. 1,021 pmol·mg protein−1·10 s−1).
- The Km values for Na-Pi cotransport remained unchanged, indicating no alteration in carrier affinity.
- Gentamicin exposure did not affect plasma parathyroid hormone, BBM glucose transport, or BBM membrane fluidity markers.
- The Vmax of BBM alkaline phosphatase was also reduced in gentamicin-exposed rats.
Conclusions:
- In utero gentamicin exposure impairs the postnatal development of renal phosphate transport capacity by reducing the maximal transport rate (Vmax) of the Na-Pi cotransporter.
- This impairment is not due to altered carrier affinity but rather a developmental defect affecting the transporter's overall function.
- Gentamicin's effects on renal phosphate handling are specific and do not broadly impact proximal tubule BBM function or membrane integrity.
Abstract:
The renal phosphate (Pi)-transporting capacity normally increases, due to increased carrier system affinity, during the third postnatal week in rats. However, the tubular Pi reabsorption of rat pups born from gentamicin-treated mothers does not increase during this period. This study determines whether exposure to gentamicin in utero selectively alters the postnatal maturation of the carrier affinity for Pi. Pi and glucose transports by proximal tubule brush-border membrane (BBM) were studied. The maximal rate of uptake (Vmax) of Na-Pi cotransport was significantly lower (536 +/- 169 pmol.mg protein-1.10 s-1; n = 6, P < 0.01) in gentamicin-exposed rats than in controls (1,021 +/- 167 pmol.mg protein-1.10 s-1, n = 6), whereas the Michaelis constant (Km) values were the same. Gentamicin exposure had no effect on plasma parathyroid hormone concentration or on BBM glucose transport activity. The total phospholipid content of BBM, their phospholipid composition, cholesterol content, and cholesterol-to-total phospholipid mole ratio were unaltered, suggesting that membrane fluidity was unchanged. The Vmax of BBM alkaline phosphatase was lower in gentamicin-exposed rats than in controls.