title: Phospholipase-A2 action and arachidonic acid metabolism in calcium-mediated parathyroid hormone secretion.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique URA 583, Université Paris V, Hospital Necker-Enfants Malades, France.
authors.forename: A
authors.initials: A
authors.lastname: Bourdeau
authors.forename: J C
authors.initials: JC
authors.lastname: Souberbielle
authors.forename: P
authors.initials: P
authors.lastname: Bonnet
authors.forename: P
authors.initials: P
authors.lastname: Herviaux
authors.forename: C
authors.initials: C
authors.lastname: Sachs
authors.forename: M
authors.initials: M
authors.lastname: Lieberherr
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D010280:Parathyroid Glands / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2; D011720:Pyrazoles / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014316:Tritium
chemical_list: D000098:Acetophenones; D044950:Flavanones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D010281:Parathyroid Hormone; D011720:Pyrazoles; D014316:Tritium; D016718:Arachidonic Acid; C006680:baicalein; D009637:Masoprocol; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; C015429:phenidone; C006821:4-bromophenacyl bromide; D002118:Calcium; D007052:Ibuprofen; D007213:Indomethacin