精氨酸升压素(4-8)对原代培养星状胶质细胞及胚胎神经元细胞中MAPK活性的影响(英文)

目的:研究精氨酸升压素(4-8)(AVP_(4-8))对来自大鼠大脑皮层和海马的原代培养星状胶质细胞及胚胎神经元细胞中促细胞分裂素活化的蛋白激酶(MAPK)活性变化的影响.同时探讨了这种影响经由的信号传递途径中可能牵涉的蛋白激酶.方法:来自大鼠脑的原代细胞培养于无血清培养基(胚胎神经元细胞)或于给药前无血清饥饿24 h,转入加药物的无钙镁磷酸缓冲液中温育,测定MAPK激酶活性.结果:(1)AVP_(4-8)能刺激原代培养的星状胶质细胞中MAPK活性但对胚胎神经元中MAPK活性没有影响.AVP_(4-8)在星状胶质细胞中诱导的MAPK活性增强作用可被AVP_(4-8)的拮抗剂ZDC(c)PR阻断.(2)MEK(MAPK/ERK激酶)的选择性抑制剂PD98059以及PKC专一性抑制剂GF109203X能消除星状胶质细胞中AVP_(4-8)诱导的活性增强作用.结论:AVP_(4-8)能以受体特异的方式激活星状胶质细胞中的MAPK活性,MEK和PKC这两个激酶参与了这个MAPK信号传递途径.AVP_(4-8)不影响原代培养胚胎神经元中的MAPK活性.

Influence of AVP4-8 on MAPK activity in astrocytic glial and fetal neuronal cells in primary culture

AIM; 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. METHODS; 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. RESULTS; The main findings were; (1) AVP4-8 induced the MAPK activity in rat brain astroglial culture but not in fetal neuronal cul-tures. And this was blocked by ZDC (C) PR, an antag-onist of AVP4-8. (2) PD98059, a potent selective in-hibitor of MAPK/ERK kinase (MEK) and GF109203X, a specific inhibitor of protein kinase C (PKC) abolished AVP4-8-evoked MAPK activity on astrocytes. CON-CLUSION; 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.