Fernandez M, Svenningsson P, Fredholm B B
Department of Physiology and Pharmacology, Divison of Molecular Neuropharmacology, Karolinska Institutet, Stockholm, Sweden.
Life Sci. 1996;58(9):769-76. doi: 10.1016/0024-3205(95)02355-0.
Changes in brain A1 and A2A receptors and in the corresponding mRNA were studied using quantitative receptor autoradiography and in situ hybridisation. [3H]-DPCPX was used as an antagonist ligand at A1 receptors and [3H]-CGS 21680 as an agonist ligand at A2A receptors. Treatment of rats with the relatively A1 receptor selective adenosine analogue R-PIA (0.3 mg/kg) for 7 days in the presence of the peripherally acting antagonist 8-p-sulfophenyltheophylline (8-PST; 10 mg/kg) caused a decrease in the binding of the A1 receptor ligand, but not in that of the A2A receptor ligand. The effect on A1 receptors was also seen in the presence of 100 microM GTP that decreases agonist binding to insignificant levels. There was no change in either A1 or A2A receptor mRNA. No significant changes were detected following administration of either R-PIA or 8-PST alone. These results thus demonstrate an effect on brain A1 receptors after systemic administration of R-PIA in the presence of a peripherally acting adenosine antagonist, demonstrating that, under these conditions, the agonist reaches receptors in significant amounts.
利用定量受体放射自显影术和原位杂交技术，研究了大脑中A1和A2A受体以及相应信使核糖核酸（mRNA）的变化。[3H]-二丙基环戊基黄嘌呤（[3H]-DPCPX）用作A1受体的拮抗剂配体，[3H]-CGS 21680用作A2A受体的激动剂配体。在存在外周作用拮抗剂8-对磺基苯甲酰茶碱（8-PST；10毫克/千克）的情况下，用相对A1受体选择性腺苷类似物R-苯基异丙基腺苷（R-PIA；0.3毫克/千克）对大鼠进行7天治疗，导致A1受体配体的结合减少，但A2A受体配体的结合未减少。在存在100微摩尔鸟苷三磷酸（GTP）的情况下也观察到了对A1受体的影响，GTP会使激动剂结合降至微不足道的水平。A1或A2A受体mRNA均无变化。单独给予R-PIA或8-PST后未检测到显著变化。因此，这些结果表明，在存在外周作用腺苷拮抗剂的情况下，全身给予R-PIA后对大脑A1受体有影响，表明在这些条件下，激动剂能大量到达受体。
