Arachidonic acid inhibits the store-operated Ca2+ current in rat liver cells

Abstract

Vasopressin and other phospholipase-C-coupled hormones induce oscillations (waves) of [Ca 2+ ] cyt (cytoplasmic Ca 2+ concentration) in liver cells. Maintenance of these oscillations requires replenishment of Ca 2+ in intracellular stores through Ca 2+ inflow across the plasma membrane. While this may be achieved by SOCs (storeoperated Ca 2+ channels), some studies in other cell types indicate that it is dependent on AA (arachidonic acid)-activated Ca 2+ channels. We studied the effects of AA on membrane conductance of rat liver cells using whole-cell patch clamping. We found no evidence that concentrations of AA in the physiological range could activate Ca 2+ -permeable channels in either H4IIE liver cells or rat hepatocytes. However, AA (1-10 µM) did inhibit (IC 50 = 2.4 + − 0.1 µM) Ca 2+ inflow through SOCs (I SOC ) initiated by intracellular application of Ins(1,4,5)P 3 in H4IIE cells. Preincubation with AA did not inhibit I SOC development, but decreased maximal amplitude of the current. Iso-tetrandrine, widely used to inhibit receptor-activation of phospholipase A 2 , and therefore AA release, inhibited I SOC directly in H4IIE cells. It is concluded that (i) in rat liver cells, AA does not activate an AA-regulated Ca 2+ -permeable channel, but does inhibit SOCs, and (ii) iso-tetrandrine and tetrandrine are effective blockers of CRAC (Ca 2+ -release-activated Ca 2+ ) channel-like SOCs. These results indicate that AA-activated Ca 2+ -permeable channels do not contribute to hormone-induced increases or oscillations in [Ca 2+ ] cyt in liver cells. However, AA may be a physiological modulator of Ca 2+ inflow in these cells.

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

“…A reciprocal regulation of AA-activated NSOCE and SOCE has been reported by several authors (36,37,69,70). It has been suggested that AA coordinates the contribution of different receptor-regulated pathways such that each is activated in a specific temporal sequence.…”

Transient receptor potential (TRP) channels, promising potential diagnostic and therapeutic tools for cancer

“…Clinicopathologic examination indicated a significant correlation between TRPV1 expression and histopathologic differentiation. Moreover, univariate analysis revealed that low levels of TRPV1 expression were associated with increased disease-free survival (63).…”

Role of intracellular calcium and phospholipase A2 in arachidonic acid-induced toxicity in liver cells overexpressing CYP2E1

“…In different cell types, free AA has been shown to induce calcium oscillations [1], to induce store operated channel (SOC)-mediated calcium entry [2], to activate selective [3] or non selective [4] calcium channels, and to trigger the release of Ca 2+ from intracellular stores [5]. In contrast, free AA has also been shown to inhibit Ca 2+ oscillations [6], to inhibit SOC-mediated Ca 2+ entry [6,7], and to fail to activate Ca 2+ permeable channels in liver cells [7].…”