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 calci um (Ca2+). Ca2+-induced transmembrane signal transduction in the parat hyroid cell is known to result in the hydrolysis of phosphatidylinosit ol bisphosphate (PIP2), generating increases in intracellular inositol phosphates, a process which is mediated by a calcium receptor. MATERl AlS AND METHODS: To determine if lithium's effect on parathyroid cell function is mediated by an alteration in Ca2+-induced hydrolysis of PI P2, inositol 4-monophosphate (IP1), and inositol 1,4,5-trisphosphate ( IP3) were measured using anion-exchange chromatography in normal and l ithium chloride (LiCl)-treated bovine parathyroid cells at Ca2+ concen trations varying from 0.5 mmol/L to 5.0 mmol/L. IP1 and IP3 concentrat ions were determined in terms of percent control, defined as the IP1 o r 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 respo nse to progressive increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L var ied 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 in creases In [IP3]/10(6) cells (mean +/- SEM) in response to increases i n 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 pretrea ted with LiCt (P >0.05). CONCLUSIONS: Our results demonstrate that LIC l does not effect Ca2+-induced hydrolysis of PIP2, suggesting that the desensitizing effect of LiCl on the parathyroid cell is not the resul t of a Ca2+ receptor-mediated phenomenon.