AJP - Endocrinology and Metabolism, Vol 263, Issue 5 E903-E912, Copyright © 1992 by American Physiological Society
Complex effects of arachidonic acid and its lipoxygenase products on cytosolic calcium in GH3 cells
P. Vacher, J. McKenzie and B. Dufy
Laboratoire de Neurophysiologie Unite de Recherche Associee, Universite de Bordeaux 2, France.
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).
