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

用Quin 2法测得大鼠脑突触体内静息游离Ca²⁺浓度([Ca²⁺]_i)为85±13 μmol·g^-1 protein. 三氟拉嗪(TFP) 1, 5和10 μmol·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65 mmol·L^-1 KCl所致突触体[Ca²⁺]_i升高, 从192±58 μmol·g^-1 protein分别达到233±63, 431±99和661±173 μmol·g^-1 protein. TFP 5,10和50 μmol·L^-1分别使突触体Ca²⁺, Mg²⁺-ATP酶活性降低31％, 41％和45％; 使Mg²⁺-ATP#FK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, 促进神经末梢释放递质.

Effect of trifluoperazine on Ca2+ level and Ca2+, Mg2+-ATPase activity in rat brain synaptosomes

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 Ca²⁺ level ([Ca²⁺]_i) and Ca²⁺, Mg²⁺-ATPase activity in rat brain synaptosomes was studied. In the Ca²⁺-free medium, resting [Ca²⁺]_i was 52±13 μmol·g^-1 protein, and TFP at 1, 5 and 10 μmol·L^-1 failed elevate the [Ca²⁺]_i. In the Ca²⁺-containing medium, the resting [Ca²⁺]_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, [Ca²⁺]_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 [Ca²⁺]_i induced by TFP is dependent on extracellular Ca²⁺ concentration. TFP 5, 10 and 50 μmol·L^-1 inhibited activities of Ca²⁺, Mg²⁺-ATPase and Mg²⁺-ATPase by 31%, 41%, 45% and 30%, 36%, 39% respectively. Ca²⁺, Mg²⁺-ATPase is a Ca²⁺-CaM- dependent ATPase. It might be that TFP inhibits Ca²⁺, Mg²⁺-ATPase ctivity by inhibiting CaM and raises the [Ca²⁺]_i, then facilitates the transmitter release.