Wang Y, Xiong Y, Du Y C
Shanghai Institute of Biochemistry, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Pharmacol Sin. 2000 Sep;21(9):802-6.
To study the effect of argipressin (4-8) (AVP4-8) on the mitogen-activated protein kinase (MAPK) activity in astroglial culture and fetal neuronal culture from rat cerebral cortex and hippocampus. Some protein kinases involved in this signal pathway were also addressed.
Rat brain primary cells were cultured in serum free medium or starved for 24 h before use. Cells were transferred to Ca2+ and Mg2+ free Dulbeco's phosphate buffer (D-PBS) with various drugs. MAPK activity was measured.
The main findings were: (1) AVP4-8 induced the MAPK activity in rat brain astroglial culture but not in fetal neuronal cultures. And this was blocked by ZDC (C) PR, an antagonist of AVP4-8. (2) PD98059, a potent selective inhibitor of MAPK/ERK kinase (MEK) and GF109203X, a specific inhibitor of protein kinase C (PKC) abolished AVP4-8-evoked MAPK activity on astrocytes.
AVP4-8 can activate the MAPK activity in astrocytes but not in fetal neuronal culture. MEK and PKC may be involved in the AVP4-8-evoked cascade.
研究精氨酸加压素(4-8)(AVP4-8)对大鼠大脑皮层和海马星形胶质细胞培养物及胎儿神经元培养物中丝裂原活化蛋白激酶(MAPK)活性的影响。同时也探讨了参与该信号通路的一些蛋白激酶。
大鼠脑原代细胞在无血清培养基中培养或在使用前饥饿24小时。将细胞转移至含有各种药物的无钙镁杜氏磷酸盐缓冲液(D-PBS)中,测定MAPK活性。
主要发现如下:(1)AVP4-8可诱导大鼠脑星形胶质细胞培养物中的MAPK活性,但在胎儿神经元培养物中无此作用。且这一作用可被AVP4-8拮抗剂ZDC(C)PR阻断。(2)MAPK/ERK激酶(MEK)的强效选择性抑制剂PD98059和蛋白激酶C(PKC)的特异性抑制剂GF109203X可消除AVP4-8诱导的星形胶质细胞MAPK活性。
AVP4-8可激活星形胶质细胞中的MAPK活性,但对胎儿神经元培养物无此作用。MEK和PKC可能参与了AVP4-8引发的级联反应。