Complex effects of arachidonic acid and its lipoxygenase products on cytosolic calcium in GH3 cells
Vacher, P.; McKenzie, J.; Dufy, B.
American Journal of Physiology 263(5 Pt 1): E903-E912
1992
ISSN/ISBN: 0002-9513 PMID: 1332497 Document Number: 389182
The mechanisms by which arachidonic acid (AA) and its metabolites stimulate prolactin release from pituitary cells are not understood. Because Ca-2+ ions are pivotal to exocytosis, we investigated the effects of AA metabolites on intracellular calcium concentration ((Ca-2+)-i) and membrane ionic currents using dual-excitation microspectrofluorimetry and whole cell patch-clamp techniques in GH-3/B6 pituitary line cells. AA (1 mu-M) had a biphasic effect on (Ca-2+)-i, mobilization of intracellular Ca-2+ followed by stimulation of Ca-2+ entry. Only the latter appeared to result from the degradation of AA through the lipoxygenase pathway. Indomethacin (Indo, 10 mu-M) and lipoxygenase products 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE, 1 mu-M), 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 Ca-2+ channels. Refilling of intracellular Ca-2+ stores, and Ca-2+ efflux, may also be stimulated. Our results demonstrate a control of (Ca-2+)-i by a second messenger (AA) and its metabolites (HETEs).