Casebolt T L, Jope R S
Department of Psychiatry, University of Alabama, Birmingham 35294.
Biol Psychiatry. 1991 Feb 1;29(3):233-43. doi: 10.1016/0006-3223(91)91285-y.
Lithium inhibits the agonist-induced hydrolysis of phosphoinositides and the synthesis of cyclic AMP (cAMP) in rat brain preparations, each of which is linked to activation of specific protein kinases. Therefore, we examined the effects of chronic lithium treatment on protein kinase activities in rat hippocampus. Chronic lithium treatment did not alter the distribution or activity of protein kinase C in hippocampal soluble or particulate fractions. However, chronic lithium treatment increased protein kinase C-mediated phosphorylation of four endogenous proteins in the soluble fraction (16,17,20,22 kD) and reduced the phosphorylation of three proteins (18,19,87 kD) in the particulate fraction. Chronic lithium treatment did not alter cAMP-dependent phosphorylation of endogenous proteins in the soluble fraction but reduced phosphorylation of two proteins (54 and 71 kD) in the particulate fractions. These results demonstrate that besides inhibiting second messenger production in brain, chronic lithium treatment also causes specific alterations in the phosphorylation of endogenous proteins.
锂可抑制大鼠脑制备物中激动剂诱导的磷酸肌醇水解以及环磷酸腺苷（cAMP）的合成，而这两者均与特定蛋白激酶的激活相关。因此，我们研究了慢性锂治疗对大鼠海马体中蛋白激酶活性的影响。慢性锂治疗并未改变海马体可溶性或颗粒性组分中蛋白激酶C的分布或活性。然而，慢性锂治疗增加了可溶性组分中蛋白激酶C介导的四种内源性蛋白（16、17、20、22 kD）的磷酸化，并降低了颗粒性组分中三种蛋白（18、19、87 kD）的磷酸化。慢性锂治疗并未改变可溶性组分中内源性蛋白的cAMP依赖性磷酸化，但降低了颗粒性组分中两种蛋白（54和71 kD）的磷酸化。这些结果表明，除了抑制脑中第二信使的产生外，慢性锂治疗还会导致内源性蛋白磷酸化的特定改变。
