Mori S, Popoli M, Brunello N, Racagni G, Perez J
Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Milan, Italy.
Neuropharmacology. 2001 Mar;40(3):448-56. doi: 10.1016/s0028-3908(00)00164-7.
Previous studies showed that the type II Ca(2+)/calmodulin- and cAMP-dependent protein kinases (CaMKII and PKA) are affected by long-term antidepressant treatment in presynaptic and somatodendritic compartments, respectively. This study describes the long-term effects of the selective noradrenaline reuptake inhibitor reboxetine on PKA and CaMKII, in both the microtubule and subsynaptosomal fractions of rat brain. Unlike other antidepressants, chronic reboxetine induced in the cerebrocortical soluble and microtubule fractions a decrease in the [(32)P]cAMP binding to the type II PKA regulatory subunit. No change in the cAMP-dependent endogenous phosphorylation of the protein substrate, microtubule-associated protein 2 was observed. In the hippocampal subsynaptosomal fractions (synaptic vesicles and synaptosomal membranes) reboxetine induced a robust increase in the activity but not in the expression of CaMKII. An increase in the calcium/calmodulin-dependent phosphorylation of presynaptic substrates was also detected. These findings showed that reboxetine modulates post-receptor signal transduction systems in rat brain.
先前的研究表明，II型钙/钙调蛋白依赖性蛋白激酶和环磷酸腺苷（cAMP）依赖性蛋白激酶（CaMKII和PKA）分别在突触前和体树突状区室受长期抗抑郁治疗的影响。本研究描述了选择性去甲肾上腺素再摄取抑制剂瑞波西汀对大鼠脑微管和突触体下组分中PKA和CaMKII的长期影响。与其他抗抑郁药不同，慢性瑞波西汀在大脑皮质可溶性和微管组分中诱导与II型PKA调节亚基结合的[(32)P]cAMP减少。未观察到蛋白底物微管相关蛋白2的cAMP依赖性内源性磷酸化有变化。在海马突触体下组分（突触小泡和突触体膜）中，瑞波西汀诱导CaMKII的活性显著增加，但未诱导其表达增加。还检测到突触前底物的钙/钙调蛋白依赖性磷酸化增加。这些发现表明，瑞波西汀可调节大鼠脑中受体后信号转导系统。
