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Multiple modulation of Na-dependent Pi uptake by cellular Ca in MDCK cells
B Escoubet1, M C Garestier, C Le Grimellec
1Department of Physiology, Faculté de Médecine X Bichat, Université Paris, France.
The American Journal of Physiology
|July 1, 1993
Summary
Phosphate deprivation lowers intracellular calcium, which is key for stimulating sodium-dependent phosphate cotransport (Na-Pi) under prolonged calcium or phosphate deficiency. Different pathways modulate Na-Pi during these depletions.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Transport Mechanisms
Background:
- The mechanisms adapting sodium-dependent phosphate cotransport (Na-Pi) to phosphate deprivation, beyond genomic regulation, are not fully understood.
- Intracellular calcium concentration's role in regulating Na-Pi during phosphate deprivation requires further investigation.
Purpose of the Study:
- To investigate the involvement of intracellular calcium concentration changes in the adaptation of Na-Pi to phosphate deprivation.
- To elucidate the relationship between calcium levels and Na-Pi activity in Madin-Darby canine kidney (MDCK) cells.
Main Methods:
- Measuring intracellular calcium concentrations under phosphate deprivation, calcium deprivation, and with TMB8 treatment.
- Assessing Na-Pi activity by measuring phosphate uptake rates.
- Investigating the role of gene transcription and protein synthesis in Na-Pi regulation.
- Utilizing the ionophore A23187 to modulate intracellular calcium levels.
Main Results:
- Phosphate deprivation and calcium deprivation significantly decreased intracellular calcium levels.
- Calcium deprivation stimulated Na-Pi by increasing phosphate affinity, with effects becoming transcription-dependent after 15 hours.
- Combined calcium and phosphate deprivation showed synergistic effects on phosphate uptake.
- TMB8 mimicked phosphate deprivation effects on Na-Pi, indicating a role for calcium modulation.
- The ionophore A23187 inhibited both basal and stimulated Na-Pi activity.
- Calcium deprivation, but not phosphate deprivation or TMB8, stimulated sodium-coupled alanine transport.
Conclusions:
- Phosphate deprivation leads to a decrease in intracellular calcium concentration.
- Reduced intracellular calcium concentration plays a crucial role in stimulating Na-Pi during prolonged phosphate or calcium deprivation.
- Phosphate and calcium deprivation modulate Na-Pi activity through distinct cellular pathways.