蛋白酪氨酸磷酸酶SHP-2在Ⅰ型代谢型谷氨酸受体诱发痛觉超敏中的作用  

Role of protein tyrosine phosphatase SHP-2 in group Ⅰ metabotropic glutamate receptors-induced allodynia

作　　者：薛曼[1] 杨云惠[1] 索占伟[1] 杨娴[1] 胡晓东[1] 

机构地区：[1]兰州大学药学院分子药理研究所,甘肃兰州730000

出　　处：《中国药理学通报》2017年第2期171-174,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No31471060)

摘　　要：目的探讨Ⅰ型代谢型谷氨酸受体(mGluRs)的痛觉调制作用与蛋白酪氨酸磷酸酶SHP-2(Src homology-2 domain-containing phosphatase-2)的关系。方法以免疫共沉淀法,研究小鼠脊髓背角SHP-2与Ⅰ型mGluRs之间的相互作用;通过测定缩足阈值,观察SHP-2抑制剂NSC-87877或SHP-2的无活性突变体SHP-2(C459S)对Ⅰ型mGluRs激动剂DHPG(50 nmol)诱发的痛觉超敏的影响。结果抗m GluR5的特异性抗体,能够从脊髓背角中免疫共沉淀SHP-2,而抗mGluR1的特异性抗体则无法沉淀出SHP-2;以NSC-87877(6 nmol)或SHP-2(C459S)抑制SHP-2的活性,可有效缓解DHPG诱发的痛觉超敏。结论 SHP-2与mGluR5存在分子间的相互结合,SHP-2的激活可能参与Ⅰ型mGluRs的痛觉调制过程。Aim To investigate whether the pain modi-fication by group I metabotropic glutamate receptors （mGluRs）required the involvement of Src homology-2 domain-containing phosphatase-2 （SHP-2 ）.Methods Co-immunoprecipitation was performed to examine the possible interaction between SHP-2 and group I mGluRs in spinal cord dorsal horn of mice.By measur-ing the paw withdrawal thresholds,the effects of SHP-2 inhibitor NSC-87877 or its catalytically inactive SHP-2 （C459S ） mutant on allodynia induced by group I mGluRs agonist DHPG （50 nmol）were observed.Re-sults Anti-mGluR5 antibody was able to co-immuno-precipitate SHP-2 from spinal dorsal horn of mice, while no SHP-2 was precipitated by anti-mGluR1 anti-body.Inactivation of SHP-2 by NSC-87877 （6 nmol） or SHP-2 （C459S ） effectively attenuated allodynia caused by DHPG.Conclusion SHP-2 can physically interact with mGluR5.The activation of SHP-2 may be necessary for group I mGluRs to process the nocicep-tive information.

关 键 词：mGluR1/5 SHP-2 磷酸酶 脊髓背角 DHPG NSC-87877 

分 类 号：R-332[医药卫生] R322.81