Nalepa Irena, Kreiner Grzegorz, Kowalska Marta, Sanak Marek, Zelek-Molik Agnieszka, Vetulani Jerzy
Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Cracow, Poland.
Eur J Pharmacol. 2002 May 31;444(3):151-9. doi: 10.1016/s0014-2999(02)01660-6.
alpha(1)-Adrenoceptors have been implicated in the mechanism of action of antidepressants, but their action on specific receptor subtypes was rarely reported. We compared now the action of two prototypic antidepressant treatments: repeated imipramine and electroconvulsive shock, on the expression of the alpha(1A)- and alpha(1B)-adrenoceptor mRNAs and on the receptor density in rats. The mRNA expression was assessed by Northern blot in the prefrontal cortex and the hippocampus, the receptor density was measured by [3H]prazosin binding in the total cerebral cortex and hippocampus. In the cortex, both treatments elevated the alpha(1A)-adrenoceptor mRNA and the expression of receptor protein. The expression of alpha(1B)-adrenoceptor mRNA remained unaffected. In contrast, in the hippocampus, the antidepressant treatments augmented the density of alpha(1A)-adrenoceptor protein without changing the level of its mRNA expression there. The results suggest that the alpha(1A)-adrenoceptor subtype is specifically involved in the mechanism of action of classical antidepressant treatments.
α（1）-肾上腺素能受体与抗抑郁药的作用机制有关，但其对特定受体亚型的作用鲜有报道。我们现在比较了两种典型抗抑郁治疗方法：重复给予丙咪嗪和电休克，对大鼠α（1A）-和α（1B）-肾上腺素能受体mRNA表达及受体密度的影响。通过Northern印迹法评估前额叶皮质和海马中的mRNA表达，通过[3H]哌唑嗪结合法测量全脑皮质和海马中的受体密度。在皮质中，两种治疗均提高了α（1A）-肾上腺素能受体mRNA及受体蛋白的表达。α（1B）-肾上腺素能受体mRNA的表达未受影响。相反，在海马中，抗抑郁治疗增加了α（1A）-肾上腺素能受体蛋白的密度，而未改变其mRNA表达水平。结果表明，α（1A）-肾上腺素能受体亚型特异性参与经典抗抑郁治疗的作用机制。
