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+). Ca2+-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. Materials and methods: To determine if lithiumʹs effect on parathyroid cell function is mediated by an alteration in Ca2+-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 (LiCI)-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 [IP1/106 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]/106 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 Ca2+-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.