Endocrinology, Vol 130, 1339-1344, Copyright © 1992 by Endocrine Society

ARTICLES

Phospholipase-A2 action and arachidonic acid metabolism in calcium- mediated parathyroid hormone secretion

A Bourdeau, JC Souberbielle, P Bonnet, P Herviaux, C Sachs and M Lieberherr
Centre National de la Recherche Scientifique URA 583, Universite Paris V, Hospital Necker-Enfants Malades, France.

The involvement of arachidonic acid (AA) and its metabolites in the control of PTH secretion by porcine parathyroid cells was investigated. Increasing the extracellular calcium concentration from 0.5 to 2 mM increased free [3H]AA release and decreased PTH secretion from labeled parathyroid cells as a function of time (1-30 min). Free [3H]AA in the medium was significantly increased (+153 +/- 6%) after 5 min, while PTH secretion was significantly decreased (-75 +/- 7%) only after 15 min, suggesting a link between the two. [3H]AA release was associated with a decrease in [3H]AA incorporated into phosphatidylinositol, phosphatidic acid, and phosphatidylcholine, suggesting that these phospholipids are the major source of AA. Exogenous phospholipase-A2 (PL-A2; 1-500 mU/ml) and AA (5-40 microM) inhibited PTH secretion in a dose-dependent manner. PTH secretion inhibited by 2 mM Ca2+ was restored by two PL-A2 inhibitors, indomethacin (30 microM) and mepacrine (50 microM). The cyclooxygenase pathway inhibitor ibuprofen (20 microM) did not restore PTH secretion of affect high Ca(2+)-, AA-, or PL-A2-inhibited PTH secretion. Two inhibitors of the lipoxygenase pathway (LO), phenidone (1 microM) and baicalein (0.1 microM), a relatively selective 12-LO inhibitor, blunted high Ca(2+)-induced inhibition of PTH secretion (+101 +/- 10% and +105 +/- 6%, respectively), but nordihydroguaiaretic acid, which inhibits the 5-LO pathway, did not restore PTH secretion inhibited by high Ca2+, AA, or PL-A2. These results suggested that AA and agents that cause its liberation inhibit PTH secretion. AA may act via the 12-LO, but not via the 5-LO or cyclooxygenase, pathway. Thus, 12-LO products may be second messengers in parathyroid cells.

This article has been cited by other articles:

				T. Drueke, D. Martin, and M. Rodriguez Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1828 - 1839. [Full Text] [PDF]

				M. Rodriguez, E. Nemeth, and D. Martin The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism Am J Physiol Renal Physiol, February 1, 2005; 288(2): F253 - F264. [Abstract] [Full Text] [PDF]

				M. Pi, R. F. Spurney, Q. Tu, T. Hinson, and L. D. Quarles Calcium-Sensing Receptor Activation of Rho Involves Filamin and Rho-Guanine Nucleotide Exchange Factor Endocrinology, October 1, 2002; 143(10): 3830 - 3838. [Abstract] [Full Text] [PDF]

				J. Silver, R. Kilav, and T. Naveh-Many Mechanisms of secondary hyperparathyroidism Am J Physiol Renal Physiol, September 1, 2002; 283(3): F367 - F376. [Abstract] [Full Text] [PDF]

				Y. Almaden, A. Canalejo, E. Ballesteros, G. Anon, S. Canadillas, and M. Rodriguez Regulation of Arachidonic Acid Production by Intracellular Calcium in Parathyroid Cells: Effect of Extracellular Phosphate J. Am. Soc. Nephrol., March 1, 2002; 13(3): 693 - 698. [Abstract] [Full Text] [PDF]

				O. Kifor, R. J. MacLeod, R. Diaz, M. Bai, T. Yamaguchi, T. Yao, I. Kifor, and E. M. Brown Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells Am J Physiol Renal Physiol, February 1, 2001; 280(2): F291 - F302. [Abstract] [Full Text] [PDF]

				E. M. Brown and R. J. MacLeod Extracellular Calcium Sensing and Extracellular Calcium Signaling Physiol Rev, January 1, 2001; 81(1): 239 - 297. [Abstract] [Full Text] [PDF]

				E. Middleton Jr., C. Kandaswami, and T. C. Theoharides The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer Pharmacol. Rev., December 1, 2000; 52(4): 673 - 751. [Abstract] [Full Text] [PDF]

				Y. ALMADÉN, A. CANALEJO, E. BALLESTEROS, G. AÑÓN, and M. RODRÍGUEZ Effect of High Extracellular Phosphate Concentration on Arachidonic Acid Production by Parathyroid Tissue In Vitro J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1712 - 1718. [Abstract] [Full Text]

				M. E. Handlogten, C. Huang, N. Shiraishi, H. Awata, and R. T. Miller The Ca2+-sensing Receptor Activates Cytosolic Phospholipase A2 via a Gqalpha -dependent ERK-independent Pathway J. Biol. Chem., April 20, 2001; 276(17): 13941 - 13948. [Abstract] [Full Text] [PDF]