Multiple modulation of Na-dependent Pi uptake by cellular Ca in MDCK cells.
The events accounting for the adaptation of the sodium-dependent phosphate cotransport (Na-Pi) to phosphate deprivation other than genomic regulation remain unknown. The involvement of changes in intracellular calcium concentration was investigated in Madin-Darby canine kidney (MDCK) cells. Calcium concentration was decreased by 15 h of phosphate deprivation (-24 to -35%) or low-calcium medium (calcium deprivation) (-45%), or 8-(N,N'-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB8) (-32%). Calcium deprivation stimulated Na-Pi (2-fold at 1 h and up to 15 h) by increasing the affinity for phosphate. Combined calcium and phosphate deprivation had more than additive effects on phosphate uptake. The effect of a 15-h calcium deprivation, but not of a 2-h one, was dependent on gene transcription and protein synthesis. TMB8 stimulated phosphate uptake similarly to phosphate deprivation (increase in maximum velocity dependent on gene transcription). The ionophore A23187 decreased basal Na-Pi as well as its stimulation by phosphate or calcium deprivation or by TMB8. Calcium deprivation stimulated (3.2-fold increase) the sodium-coupled alanine transport, whereas phosphate deprivation and TMB8 did not. We conclude that 1) phosphate deprivation decreases intracellular calcium concentration, 2) low intracellular calcium concentration is instrumental in the stimulation by prolonged calcium or phosphate deprivation of Na-Pi, and 3) phosphate or calcium deprivation modulates Na-Pi through different cellular pathways.
Escoubet
B
B
Department of Physiology, Faculté de Médecine X Bichat, Université Paris, France.
Garestier
M C
MC
Le Grimellec
C
C
Amiel
C
C
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D010710:Phosphates / Q000172:deficiency / Q000493:pharmacokinetics*; D012964:Sodium / Q000502:physiology*
D002121:Calcium Channel Blockers; D003839:Deoxyadenosines; D010710:Phosphates; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003513:Cycloheximide; D012964:Sodium; D002118:Calcium