Effect of high extracellular phosphate concentration on arachidonic acid production by parathyroid tissue in vitro

Recent in vivo and in vitro studies show that high phosphate directly stimu lates parathyroid hormone (PTH) secretion. However, little is known about t he intracellular signaling system involved in the regulation of PTH secreti on by extracellular phosphate. High extracellular calcium is coupled to the activation of phospholipase A(2) (PLA(2)) and the formation of arachidonic acid (AA), a potent inhibitor of PTH release. The present study was design ed to evaluate whether a high phosphate concentration has an effect on the PLA(2)-AA pathway in parathyroid cells. In vitro experiments were performed in parathyroid tissue obtained from normal rats and dogs. AA production wa s measured in parathyroid tissue in response to 1- and 4-mM phosphate conce ntration and after addition of PLA(2) to the medium. To determine whether t he effect of phosphate on AA production in parathyroid cells was tissue spe cific, separate experiments were performed to test the effect of phosphate in rat adrenal glomerulosa cells, which are known to increase AA production in response to angiotensin II. The effect of sulfate, an ion with chemical characteristics similar to phosphate, on PTH secretion was also evaluated, In parathyroid tissue, a high phosphate concentration decreased the high c alcium-induced AA production. This effect of phosphate was associated with an increase in PTH secretion. The addition of AA reversed the stimulatory e ffect of phosphate on PTH secretion. In another type of APL-responsive tiss ue, the adrenal glomerulosa, a high phosphate concentration did not affect the production of AA when stimulated by angiotensin II. In a normal phospha te concentration, the addition of PLA(2) stimulated AA production and decre ased the PTH secretion. However, in a 4-mM phosphate concentration, the add ition of PLA(2) did not reduce PTH secretion and did not stimulate AA produ ction. Finally, sulfate did not affect PTH secretion. In conclusion, a high phosphate concentration affects the production of AA by parathyroid tissue . This effect of phosphate may be the mechanism by which a high phosphate c oncentration stimulates PTH secretion.