Accumulation of glycerophosphocholine (GPC) by renal cells: osmotic regulation of GPC:choline phosphodiesterase.
Although GPC has long been recognized as a degradation product of phosphatidylcholine, only recently is there wide appreciation of its role as a compatible and counteracting osmolyte that protects cells from osmotic stress. GPC is osmotically regulated in renal cells. Its level varies directly with extracellular osmolality. Cells in the kidney medulla in vivo and in renal epithelial cell cultures (MDCK) accumulate large amounts of GPC when exposed to high concentrations of NaCl and urea. Osmotic regulation of GPC requires choline in the medium, presumably as a precursor for synthesis of GPC. Choline transport into the cells, however, is not osmoregulated. The purpose of the present studies was to use MDCK cell cultures as a defined model to distinguish whether osmotically induced accumulation of GPC results from increased GPC synthesis or decreased GPC disappearance. The rate of incorporation of 14C from [14C]choline into GPC, the steady-state GPC synthesis rate, and the activity of phospholipase A2 (which can catalyze a step in the synthesis of GPC from phosphatidylcholine) are not increased by high NaCl and urea. In fact all are decreased by approximately one-third. Therefore, we find no evidence that high NaCl and urea increases the GPC synthesis rate. On the other hand, the rate coefficient for cellular GPC disappearance and the activity of GPC:choline phosphodiesterase (EC 3.1.4.2), which catalyzes degradation of GPC, are decreased by approximately two-thirds by high NaCl and urea. We conclude that high NaCl and urea increase the level of GPC by inhibiting its enzymatic degradation.
Zablocki
K
K
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Miller
S P
SP
Garcia-Perez
A
A
Burg
M B
MB
D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D004285:Dogs; D005997:Glycerylphosphorylcholine / Q000378:metabolism*; D007668:Kidney / Q000502:physiology*; D007700:Kinetics; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D002250:Carbon Radioisotopes; D012965:Sodium Chloride; D005997:Glycerylphosphorylcholine; D014508:Urea; D010741:Phospholipases A; D054467:Phospholipases A2; D010727:Phosphoric Diester Hydrolases; C061931:glycerophosphocholine cholinephosphodiesterase; D002794:Choline