Investigation of calcium-induced hydrolysis of phosphoinositides in normal and lithium-treated parathyroid cells.
BACKGROUND
Lithium-induced hyperparathyroidism is characterized by a reduction in parathyroid sensitivity to changes in extracellular calcium (Ca2+). Ca(2+)-induced transmembrane signal transduction in the parathyroid cell is known to result in the hydrolysis of phosphatidylinositol bisphosphate (PIP2), generating increases in intracellular inositol phosphates, a process which is mediated by a calcium receptor.


METHODS
To determine if lithium's effect on parathyroid cell function is mediated by an alteration in Ca(2+)-induced hydrolysis of PIP2, inositol 4-monophosphate (IP1), and inositol 1,4,5-trisphosphate (IP3) were measured using anion-exchange chromatography in normal and lithium chloride (LiCl)-treated bovine parathyroid cells at Ca2+ concentrations varying from 0.5 mmol/L to 5.0 mmol/L. IP1 and IP3 concentrations were determined in terms of percent control, defined as the IP1 or IP3 concentration at an [Ca2+] of 0.5 mmol/L.


RESULTS
Increases in [IP1]/10(6) cells (mean +/- standard error of the mean [SEM]) in response to progressive increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L varied from 825 +/- 228 to 4,474 +/- 382 in control cells versus 1,139 +/- 243 to 4,689 +/- 630 in cells pretreated with LiCl (P > 0.05). The increases in [IP3]/10(6) cells (mean +/- SEM) in response to increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L, varied from 146 +/- 14 to 385 +/- 35 in control cells versus 134 +/- 16 to 327 +/- 55 in cells pretreated with LiCl (P > 0.05).


CONCLUSIONS
Our results demonstrate that LiCl does not effect Ca(2+)-induced hydrolysis of PIP2, suggesting that the desensitizing effect of LiCl on the parathyroid cell is not the result of a Ca2+ receptor-mediated phenomenon.
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D006961:Hyperparathyroidism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000378:metabolism; D007295:Inositol Phosphates / Q000032:analysis / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000032:analysis / Q000378:metabolism; D010716:Phosphatidylinositols / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C045537:inositol 4-phosphate; D015544:Inositol 1,4,5-Trisphosphate; D018021:Lithium Chloride; D002118:Calcium