抗抑郁剂对大鼠大脑皮层腺苷酸环化酶活性的影响  

Effect of antidepressants on adenylate cyclase activity of rat cerebral cortex

作　　者：李云峰[1] 龚正华[1] 张汉霆[1] 罗质璞[1] 

机构地区：[1]军事医学科学院毒物药物研究所

出　　处：《军事医学科学院院刊》1999年第2期130-132,共3页Bulletin of the Academy of Military Medical Sciences

摘　　要：目的：观察３类抗抑郁剂对大鼠大脑皮层腺苷酸环化酶（ａｄｅｎｙｌａｔｅｃｙｃｌａｓｅ，ＡＣ）活性的影响，探讨药物的受体后作用机制。方法：提取大脑皮层突触膜，用现有的３类经典抗抑郁剂丙米嗪及阿米替林（三环类）、氟西汀（选择性５－ＨＴ重吸收抑制剂）、吗氯贝胺（单胺氧化酶抑制剂）与突触膜直接进行孵育，观察ＡＣ活性改变。结果：丙米嗪、阿米替林及氟西汀均可使ＡＣ激活，量效关系显著，而吗氯贝胺却无此作用，非抗抑郁剂苯丙胺（也是递质重吸收抑制剂）对ＡＣ活性也无影响。结论：三环类抗抑郁剂及选择性５－ＨＴ重吸收抑制剂的作用可能与信号转导系统中ＡＣ－ｃＡＭＰ通路强化有关，而吗氯贝胺可能有其他的作用方式。抗抑郁剂对神经元突触后膜有直接作用，并暗示是通过直接强化Ｇｓ等Ｇ蛋白的功能加强了Ｇｓ对ＡＣ的激活作用。Objective: To observe the effect of 3 kinds of antidepressants on adenylate cyclase(AC) of rat's cerebral cortex and analyze the postreceptor biochemical mechanism of the drugs. Methods: The synaptic membrane of rat's cerebral cortex was extracted and incubated with current three classes of antidepressants, then, AC activity was examined. Results: Imipramineamitriptyline (TCAs), fluoxetine (SSRIs) could activate AC on synaptic membrane in a dosedependent manner, while moclobemide (MAO inhibitor) had no such effect.Further more, amphetamine (a monoamine reuptake inhibitor,but not an antidepressant) administration did not enhance AC activity either. Conclusion: The effect of TCAs and SSRIs is related to the enhancement of ACcAMP pathway, while MAO inhibitor has special action pattern which is different from that of TCAs and SSRIs. The results indicated that antidepressants have direct action on postsynaptic membrane. Furthermore, these data contribute to the suggestion that antidepressants increase the coupling and interaction between Gs protein and AC through enhancing Gs activity in an acute way.

关 键 词：抗抑郁剂 腺苷酸环化酶 突触膜 信号转导 

分 类 号：R971.43[医药卫生—药品]