Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potass

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:robert198121
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Aim: To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch-induced increase in calcium-activated potassium currents (I_(KCa)) in gastric myocytes. Methods: Membrane currents were recorded by using a conventional whole cell patch-clamp technique in gastric myocytes isolated with collagenase. Results: Hyposmotic membrane stretch and AA increased both I_(K(Ca)) and spontaneous transient outward currents significantly. Exogenous AA could potentiate the hyposmotic membrane stretch-induced increase in I_(K(Ca)) The hyposmotic membrane stretch-induced increase in _(K(Ca)) was significantly suppressed by dimethyleicosadienoic acid (100 μmol/L in pipette solution), an inhibitor of phospholipase A_2. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA and hyposmotic membrane stretch-induced increases in I_(K(Ca)). External calcium-free or gadolinium chloride, a blocker of stretch-activated channels, blocked the AA-induced increase in I_(K(Ca)) significantly, but it was not blocked by nicardipine, an L-type calcium channel blocker. Ryanodine, a calcium-induced calcium release agonist, completely blocked the AA-induced increase in _(K(Ca)); however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA-induced increase in I_(K(Ca)). Conclusion: Hyposmotic membrane stretch may activate phospholipase A_2, which hydrolyzes membrane phospholipids to ultimately produce AA; AA as a second messenger mediates Ca~(2+) influx, which triggers Ca~(2+)-induced Ca~(2+) release and elicits activation of I_(K(Ca)) in gastric antral circular myocytes of the guinea pig. Aim: To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch-induced increase in calcium-activated potassium currents (I_ (KCa)) in gastric myocytes. Methods: Membrane currents were recorded by using a conventional whole cell patch-clamp technique in gastric myocytes isolated with collagenase. Results: Hyposmotic membrane stretch and AA increased both I_ (K (Ca)) and spontaneous transient outward currents significantly. Exogenous AA could potentiate the hyposmotic membrane stretch-induced increase in I_ (K ( Ca 2+) Nordinhydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA (Ca (Ca))) was significantly suppressed by dimethyleicosadienoic acid (100 μmol / L in pipette solution), an inhibitor of phospholipase A_2 External calcium-free or gadolinium chloride, a blocker of stretch-activated channels, blocked the AA-induced i (K (Ca)) and hyposmotic membrane stretch-induced increases in I_ Ryanodine, a calcium-induced calcium release agonist, completely blocked the AA-induced increase in _ (K (Ca) ); however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA-induced increase in I_ (K (Ca)). Conclusion: Hyposmotic membrane stretch may activate phospholipase A_2, which hydrolyzes membrane phospholipids to ultimately produce AA ; AA as a second messenger mediates Ca ~ (2+) influx, which triggers Ca ~ (2 +) - induced Ca ~ (2+) release and elicits activation of I_ (K (Ca)) in gastric antral circular myocytes of the guinea pig
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