Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex
Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex
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DOI：
10.1016/j.biopsych.2006.03.022
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发表时间：
2007-01-15
影响因子：
10.6
通讯作者：
Rao, Jagadeesh S.
中科院分区：
文献类型：
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作者：
Ertley, Renee N.;Bazinet, Richard P.;Rao, Jagadeesh S.
工作背景：G蛋白受体激酶（GRKs）是参与激动剂激活的G蛋白偶联受体（GPCR）的同源脱敏的丝氨酸/苏氨酸激酶家族。G蛋白偶联受体超敏性，可能是情感障碍降低的结果。GRK，已建议在方法：我们使用免疫印迹法，以确定是否慢性，治疗相关剂量的锂（Li+），卡马西平（CBZ），丙戊酸盐（VPA），将增加GRK 2/3蛋白水平在大鼠额叶cortic.Results：慢性Li+（24%）和CBZ（44%）显着增加GRK 3的膜，但不是胞浆分数。慢性VPA对GRK 3无影响。所有治疗组的G蛋白受体激酶2蛋白水平均无变化。GRK 3膜胞浆比显着增加Li+和CBZ治疗rats.Conclusions：这些结果表明，长期管理Li+和CBZ，但不VPA，增加GRK 3从胞浆到膜的易位，可能纠正双相情感障碍的GPCRs的超敏感性。
Background: G-protein receptor kinases (GRKs) are a family of serine/threonine kinases involved in the homologous desensitization of agonist activated G-protein coupled receptors (GPCRs). G-protein coupled receptor supersensitivity, possibly as a result of decreased in affective disorders. GRK, has been suggested inMethods: We used immunobloting to determine if chronic, therapeutically relevant doses of lithium (Li+), carbamazepine (CBZ), and valproate (VPA), would increase GRK2/3 protein levels in rat frontal cortex.Results: Chronic Li+ (24%) and CBZ (44%) signficantly increased GRK3 in the membrane but not cytosol fractions. Chronic VPA bad no effect on GRK3. G-protein receptor kinase 2 protein levels were unchanged by all treatments. The GRK3 membrane to cytosol ratio was increased significantly in Li+ and CBZ treated rats.Conclusions: These results show that chronically administered Li+ and CBZ, but not VPA, increase the translocation of GRK3 from cytosol to membrane, possibly correcting supersensitivity of GPCRs in bipolar disorder.