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 stimulates parathyroid hormone (PTH) secretion. However, little is known about the intracellular signaling system involved in the regulation of PTH secretion 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 designed 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 was measured in parathyroid tissue in response to 1- and 4-mM phosphate concentration and after addition of PLA(2) to the medium. To determine whether the effect of phosphate on AA production in parathyroid cells was tissue specific, 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 calcium-induced AA production. This effect of phosphate was associated with an increase in PTH secretion. The addition of AA reversed the stimulatory effect of phosphate on PTH secretion. In another type of AA-responsive tissue, the adrenal glomerulosa, a high phosphate concentration did not affect the production of AA when stimulated by angiotensin II. In a normal phosphate concentration, the addition of PLA(2) stimulated AA production and decreased the PTH secretion. However, in a 4-mM phosphate concentration, the addition of PLA(2) did not reduce PTH secretion and did not stimulate AA production. 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 concentration stimulates PTH secretion.
Almadén
Yolanda
Y
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.
Canalejo
Antonio
A
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.
Ballesteros
Evaristo
E
Department of Physical and Analytical Chemistry, Technical University School at Linares, University of Jaén, Spain.
Añón
Gracia
G
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.
Rodríguez
Mariano
M
Research Unit and Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain.
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010741:Phospholipases A / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology
D010281:Parathyroid Hormone; D010710:Phosphates; D013431:Sulfates; D016718:Arachidonic Acid; D010741:Phospholipases A; D002118:Calcium