Gubits R M, Smith T M, Fairhurst J L, Yu H
Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Brain Res Mol Brain Res. 1989 Jul;6(1):39-45. doi: 10.1016/0169-328x(89)90026-0.
Recent evidence supports a role for transient c-fos expression as one step in signalling pathways by which membrane receptor-ligand interactions are transduced into appropriate intracellular responses. The activity of adrenergic receptors is mediated by second messenger systems which include ion fluxes, changes in cAMP concentration and enhanced phosphoinositide turnover. In order to determine if C-fos induction was also a step in adrenergic signal transduction in the brain, we performed in vivo studies with drugs specific for different adrenergic receptor types. Unexpectedly, we found that the stress associated with a single intraperitoneal (i.p.) injection of drug vehicle produced a transient increase (averaging 4.0-fold) in c-fos mRNA levels in rat brain. Injection of the alpha 2-adrenoreceptor antagonist, yohimbine, produced a transient increase which was larger in magnitude (averaging 9.6-fold) and longer in duration than that produced by injection of the drug vehicle alone. In experiments designed to ask whether either of these inductions was mediated by specific types of adrenergic receptors, we found that the alpha 2- and beta-adrenoreceptors were involved in both responses, while the alpha 1-receptor played a role in mediating the yohimbine induction, but no detectable role in the solvent induction. One hypothesis consistent with our results is that the norepinephrine (NE) released due to the stress associated with an i.p. injection interacts with postsynaptic beta-adrenergic receptors, resulting in the observed c-fos mRNA induction. When the negative feedback effect of NE, mediated by presynaptic alpha 2-receptors, is blocked by yohimbine, the postsynaptic response is enhanced and prolonged.
最近的证据支持瞬时c-fos表达在信号通路中发挥作用，这是膜受体-配体相互作用转化为适当细胞内反应的一个步骤。肾上腺素能受体的活性由第二信使系统介导，该系统包括离子通量、cAMP浓度变化和增强的磷酸肌醇周转率。为了确定C-fos诱导是否也是大脑中肾上腺素能信号转导的一个步骤，我们使用针对不同肾上腺素能受体类型的特异性药物进行了体内研究。出乎意料的是，我们发现单次腹腔注射药物赋形剂所产生的应激导致大鼠脑中c-fos mRNA水平瞬时升高（平均为4.0倍）。注射α2-肾上腺素能受体拮抗剂育亨宾产生的瞬时升高幅度更大（平均为9.6倍），持续时间比单独注射药物赋形剂更长。在旨在探究这些诱导是否由特定类型的肾上腺素能受体介导的实验中，我们发现α2-和β-肾上腺素能受体均参与了这两种反应，而α1-受体在介导育亨宾诱导中发挥作用，但在溶剂诱导中未检测到作用。与我们的结果一致的一种假设是，由于腹腔注射相关应激而释放的去甲肾上腺素（NE）与突触后β-肾上腺素能受体相互作用，导致观察到的c-fos mRNA诱导。当由突触前α2-受体介导的NE负反馈效应被育亨宾阻断时，突触后反应增强并延长。
