期刊
NEURON GLIA BIOLOGY
卷 6, 期 2, 页码 113-125出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1740925X10000141
关键词
Citalopram; cPLA(2); ERK; fluorescence-activated cell sorting; paroxetine
资金
- National Natural Science Foundation of China [30670651, 30770667, 30711120572]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS050315] Funding Source: NIH RePORTER
In well-differentiated primary cultures of mouse astrocytes, which express no serotonin transporter (SERT), the 'serotonin-specific reuptake inhibitor' (SSRI) fluoxetine leads acutely to 5-HT2B receptor-mediated, transactivation-dependent phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) with an EC50 of similar to 5 mu M, and chronically to ERK1/2 phosphorylation-dependent upregulation of mRNA and protein expression of calcium-dependent phospholipase A(2) (cPLA(2)) with ten-fold higher affinity. This affinity is high enough that fluoxetine given therapeutically may activate astrocytic 5-HT2B receptors (Li et al., 2008, 2009). We now confirm the expression of 5-HT2B receptors in astrocytes freshly dissociated from mouse brain and isolated by fluorescence-activated cell sorting (FACS) and investigate in cultured cells if the effects of fluoxetine are shared by all five conventional SSRIs with sufficiently high affinity to be relevant for mechanism(s) of action of SSRIs. Phosphorylated and total ERK1/2 and mRNA and protein expression of cPLA(2a) were determined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Paroxetine, which differs widely from fluoxetine in affinity for SERT and for another 5-HT2 receptor, the 5-HT2C receptor, acted acutely and chronically like fluoxetine. One micromolar of paroxetine, fluvoxamine or sertraline increased cPLA(2a) expression during chronic treatment; citalopram had a similar effect at 0.1-0.5 mu M; these are therapeutically relevant concentrations.
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