Involvement of aputativeG-protein-coupled receptor and a branching pathway in argipresin(4-8)signal transduction in rat hippocampus  

Involvement of a putative G protein coupled receptor and a branching pathway in argipressin (4-8) signal transduction in rat hippocampus

作　　者：乔利亚[1] 杜雨苍[1] 

机构地区：[1]中国科学院上海生物化学研究所

出　　处：《中国药理学报》1998年第1期15-19,共5页Acta Pharmacologica Sinica

摘　　要：目的：研究精加压素片段（４－８）在大鼠海马中的信号跨膜转导．方法：比较大鼠海马切片在药物刺激后的ＭＡＰＫ活性（ＭＫ）和ＣａＭＫⅡ自身磷酸化水平（ＫⅡ）的变化．结果：（４－８）的拮抗剂ＺＤＣ（Ｃ）ＰＲ及ＧＰＣＲ的抑制剂ＰＴＸ分别都能阻断（４－８）引起的（ＭＫ）和（ＫⅡ）的增高，但都不影响ＡＶＰ诱导的（ＭＫ）变化；ＰＭＢ抑制（４－８）诱导的（ＭＫ）增高而对（ＫⅡ）无影响；ＴＰＡ单独可以刺激（ＭＫ）增高达（４－８）的（ＭＫ）水平，同时使（ＫⅡ）停留在对照水平；（ＭＫ）的增高不被ＫＮ６２阻断；与ＡＶＰ不同，（４－８）不影响ｃＡＭＰ水平．结论：精加压素片段（４－８）通过未知ＧＰＣＲ和Ｇ０介导一分支信号途径．AIM: To study the signal transduction pathway induced by argipressin(4-8) (AVP 4-8 ) in rat hippocampus. METHODS: Rat hippocampi were sectioned transversely at 300 μm with a tissue chopper and transferred to fresh incubation solution circulated with a humidified gas mixture of 95 % O 2+5 % CO 2 at 36±0 5 ℃. After incubation with various drugs, MAP kinase (MAPK) activity and Ca 2+ /calmodulin dependent protein kinase Ⅱ ( CaMKⅡ ) auto￣phos￣phorylation were measured. RESULTS: The main findings are: (1) The AVP 4-8 stimulated MAPK activity and the CaMKⅡ autophosphorylation were blocked by ZDC(C)PR, an antagonist of AVP 4-8 , and also completely inhibited by pertussis toxin, a selective inhibitor of the G protein coupled receptor (GPCR). But, AVP induced MAPK activation was not sensitive to ZDC(C)PR or PTX. (2) Polymyxin B (PMB), an inhibitor of protein kinase C (PKC), markedly suppressed the peptide activation of MAPK, but did not affect CaMKⅡ autophosphorylation. Phorbol myristate acetate (TPA), an activator of PKC, elicited an increase of MAPK activity, but did not further influence the level of AVP 4-8 enhanced MAPK activity; Nevertheless, the extent of CaMKⅡ activation was attenuated by TPA. (3) The enhancement of MAPK activity was not reduced by KN 62, a specific inhibitor of CaMKⅡ . (4) AVP 4-8 did not show any influence on cAMP production. CONCLUSION: AVP 4-8 stimulated signal transduction via a GPCR and a branching pathway in rat hippocampus.

关 键 词：精氨酸 加压素 受体 海马 蛋白激酶类 

分 类 号：R972.4[医药卫生—药品]