溶血磷脂酸对大鼠心肌细胞膜Na^+-Ca^(2+)交换的影响

Influence of lysophosphatidic acid on Na^+-Ca^(2+) exchange activity in rat cardiac sarcolemma

本研究采用蔗糖梯度离心法制各大鼠心肌细胞膜，观察溶血磷脂酸（ ＬＰＡ）对心肌细胞膜 Ｎａ~＋－Ｃａ^(２＋)交换的影 响。结果发现ＬＰＡ（１～２０ｎｍｏｌ／Ｌ）呈剂量依赖性和时间依赖性刺激Ｎａ~＋一Ｃａ^（２＋）交换活性增加。Ｇｐｐ（ＮＨ）ｐ呈剂量依赖 性替代ＬＰＡ刺激的Ｎａ~＋－Ｃａ^(２＋)交换活性；ＰＴＸ可抑制ＬＰＡ对Ｎａ~＋－Ｃａ^(２＋)交换的激活；Ｇｅｎｉｓｔｅｉｎ，Ｐｒｏｐｒａｎｏｌｏｌ，Ｐｒａｚｏｓｉｎ，Ａｔｒｏｐｉｎｅ，Ｌｏｓａｒｔａｎ，ＢＱ１２３和磷脂酰胆碱对ＬＰＡ诱导的Ｎａ~＋－Ｃａ~２＋交换活性无影响，而磷脂酰丝氨酸可增加对照和ＬＰＡ 两组的 Ｎａ~＋－Ｃａ^(２＋)交换活性。这些结果表明 ＬＰＡ可通过 ＰＴＸ敏感的 Ｇ蛋白刺激大鼠心肌细胞膜 Ｎａ~＋－Ｃａ^(２＋)交换活性。

Sprague-Dawley rat cardiac sarcolemmal membrane was prepared by the sucrose gradient centrifugation and Influence of Lysophosphatidic acid (LPA ) on Na^+-Ca^2+ exchange activity in rat cardiac sarcolemma was investigated. The results showed that LPA stimulated Na^+-Ca^2+ exchange activity in a dose-dependent manner from 1-20nmol/L and LPA-stimulated Na^+-Ca^2+ exchange activity increased with time and to the maximum at about 5 see. Activation of Na^+Ca^2+ exchange by LPA was displaced by Gpp(NH)p in dose-dependent manner. The activation of Na^+-Ca^2+ exchange by LPA was inhibited by pertussis (PTX). LPA-induced Na^+-Ca^2+ exchange activity was not affected by Genistein, Propranolol, Prazosin, Atropine, Losartan or BQ123. Phospholipid phosphatedylserine increased Na^+-Ca^2+ exchange activity in both control group and LPA treated group while phospholipid phosphatidylserine increased Na^+-Ca^2+ exchange activity in both control group and LPA treated group while phospholipid phosphatidylcholine did not significantly affect Na^+-Ca^2+ exchange activity in both groups. These findings indicate that LPA stimulates Na^+-Ca^2+ exchange activity in rat heart sarcolemma by a PTX-sensitive G protein. The activation of Na^+-Ca^2+ exchange by LPA is associated with the membrane phospholipid and is not related to tyrosine protein kinase, β-adrenoceptor, α,-adrenoceptor, muscarinic receptor, angiotensin Ⅱ receptor (AT1 ) and endothelin A receptor.