三氟拉嗪对大鼠脑突触体内Ca2＋水平和Ca2＋，Mg2＋─ATP酶活性的作用

Effect of trifluoperazine on Ca 2+ level and Ca 2+ , Mg 2+ ATPase activity in rat brain synaptosomes 1

用Ｑｕｉｎ２法测得大鼠脑突触体内静息游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）为８５±１３μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ．三氟拉嗪（ＴＦＰ）１，５和１０μｍｏｌ·Ｌ－１对静息突触体［Ｃａ２＋］ｉ无明显影响，但能以剂量依赖方式增高６５ｍｍｏｌ·Ｌ－１ＫＣｌ所致突触体［Ｃａ２＋］ｉ升高，从１９２±５８μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ分别达到２３３±６３，４３１±９９和６６１±１７３μｍｏｌ·ｇ－１ｐｒｏｔｅｉｎ．ＴＦＰ５，１０和５０μｍｏｌ·Ｌ－１分别使突触体Ｃａ２＋，Ｍｇ２＋－ＡＴＰ酶活性降低３１％，４１％和４５％；使Ｍｇ２＋－ＡＴＰ酶活性降低３０％，３６％和３９％，提示ＴＦＰ可能是通过抑制钙调素，进而抑制Ｃａ２＋，Ｍｇ２＋－ＡＴＰ酶活性，使突触体［Ｃａ２＋］ｉ升高。

To elicit the correlation between facilitatory effect of trifluoperazine (TFP) on the adrenergic transmitter release and calmodulin (CaM) inhibition, the effect of TFP, a CaM inhibitor, on free Ca 2+ level ([Ca 2+ ] i) and Ca 2+ , Mg 2+ ATPase activity in rat brain synaptosomes was studied. In the Ca 2+ free medium, resting [Ca 2+ ] i was 52±13 μmol·g -1 protein, and TFP at 1, 5 and 10 μmol·L -1 failed elevate the [Ca 2+ ] i. In the Ca 2+ containing medium, the resting [Ca 2+ ] i was 83±13 μmol·g -1 protein. When stimulated with KCl (65 mmol·L -1 )+TFP 0, 1, 5 and 10 μmol·L -1 , [Ca 2+ ] i was dose dependently elevated to 192±58, 233±63, 431±99 and 661±173 μmol·g -1 protein respectively. It seems likely that elevation of [Ca 2+ ] i induced by TFP is dependent on extracellular Ca 2+ concentration. TFP 5, 10 and 50 μmol·L -1 inhibited activities of Ca 2+ , Mg 2+ ATPase and Mg 2+ ATPase by 31%, 41%, 45% and 30%, 36%, 39% respectively. Ca 2+ , Mg 2+ ATPase is a Ca 2+ CaM dependent ATPase. It might be that TFP inhibits Ca 2+ , Mg 2+ ATPase activity by inhibiting CaM and raises the [Ca 2+ ] i, then facilitates the transmitter release.