title: Complex effects of arachidonic acid and its lipoxygenase products on cytosolic calcium in GH3 cells.
abstract: The mechanisms by which arachidonic acid (AA) and its metabolites stimulate prolactin release from pituitary cells are not understood. Because Ca2+ ions are pivotal to exocytosis, we investigated the effects of AA metabolites on intracellular calcium concentration ([Ca2+]i) and membrane ionic currents using dual-excitation microspectrofluorimetry and whole cell patch-clamp techniques in GH3/B6 pituitary line cells. AA (1 microM) had a biphasic effect on [Ca2+]i, mobilization of intracellular Ca2+, followed by stimulation of Ca2+ entry. Only the latter appeared to result from the degradation of AA through the lipoxygenase pathway. Indomethacin (Indo, 10 microM) and lipoxygenase products 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE, 1 microM), increased action potential duration (12-HETE) or frequency (5- and 15-HETE, Indo). These effects depended on inhibition of d-tubocurarine- or tetraethylammonium-sensitive K+ conductances and stimulation of voltage-dependent Ca2+ channels. Refilling of intracellular Ca2+ stores, and Ca2+ efflux, may also be stimulated. Our results demonstrate a control of [Ca2+]i by a second messenger (AA) and its metabolites (HETEs).
authors.affiliation: Laboratoire de Neurophysiologie Unité de Recherche Associée, Université de Bordeaux 2, France.
authors.forename: P
authors.initials: P
authors.lastname: Vacher
authors.forename: J
authors.initials: J
authors.lastname: McKenzie
authors.forename: B
authors.initials: B
authors.lastname: Dufy
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D004553:Electric Conductivity; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D009994:Osmolar Concentration; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011188:Potassium; D002118:Calcium; D014403:Tubocurarine; D007213:Indomethacin