Nehlig A, Daval J L, Boyet S
INSERM U 272, Université de Nancy I, France.
Eur J Pharmacol. 1994 Jun 2;258(1-2):57-66. doi: 10.1016/0014-2999(94)90057-4.
The quantitative [14C]2-deoxyglucose autoradiographic technique was applied to the measurement of the cerebral metabolic effects of adenosine A1 and A2 receptor agonists and antagonists in adult rats. The adenosine A1 receptor agonist and antagonist, 2-chloro-N6-cyclopentyladenosine (CCPA) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as the adenosine A2 receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-5'-ethylcarboxamidoadenosin e (CGS 21680), were injected at the dose of 0.01 mg/kg. The adenosine A2 receptor antagonist, 3,7-dimethyl-1-proparglyxanthine (DMPX) was injected at the dose of 0.3 mg/kg. These doses were chosen in accordance with the known affinity of the drugs for their respective receptor and to avoid peripheral effects. The adenosine A1 receptor agonist, CCPA, induced decreases in glucose utilization in three brain areas, the globus pallidus and two hypothalamic nuclei. The adenosine A2 receptor agonist, CGS 21680, induced more general depressant effects on energy metabolism which were significant in 17 brain areas, such as cerebral cortex, hippocampal and white matter regions plus motor and limbic structures. The adenosine A2 receptor antagonist, DMPX, decreased glucose utilization in the globus pallidus while increasing energy metabolism in the cochlear nucleus. The adenosine A1 receptor antagonist, DPCPX, depressed glucose utilization in the globus pallidus and dentate gyrus, and increased rates of energy metabolism in six regions, mainly hypothalamic, thalamic areas and in the cochlear nucleus. There was a mismatch between cerebral metabolic consequences of adenosine A1 and A2 receptor agonists and the localization of corresponding adenosine receptors. The metabolic effects of the adenosine A2 receptor agonist and antagonist were consistent with the known involvement of that type of receptor in the control of locomotion and its effects on neuronal firing in the hippocampus and cerebral cortex. The effects of the adenosine A1 receptor agonist were very discrete and mostly related to the transient decrease in blood pressure induced by the drug. The increases in glucose utilization induced in limbic regions by the adenosine A1 receptor antagonist are probably linked to the regulation by adenosine of arousal and cardiorespiratory function. These results are in good agreement with the neuroregulatory function of the adenosine system as previously shown by other methods.
采用定量[14C]2-脱氧葡萄糖放射自显影技术，测定成年大鼠中腺苷A1和A2受体激动剂及拮抗剂对脑代谢的影响。分别以0.01mg/kg的剂量注射腺苷A1受体激动剂和拮抗剂2-氯-N6-环戊基腺苷（CCPA）和8-环戊基-1,3-二丙基黄嘌呤（DPCPX），以0.3mg/kg的剂量注射腺苷A2受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤（DMPX）。腺苷A2受体激动剂2-[对-(2-羧乙基)苯乙基氨基]-5'-乙基甲酰胺基腺苷（CGS 21680）的注射剂量为0.01mg/kg。这些剂量是根据药物对各自受体的已知亲和力选择的，以避免外周效应。腺苷A1受体激动剂CCPA可使三个脑区（苍白球和两个下丘脑核）的葡萄糖利用率降低。腺苷A2受体激动剂CGS 21680对能量代谢产生更广泛的抑制作用，在17个脑区（如大脑皮层、海马和白质区域以及运动和边缘结构）具有显著意义。腺苷A2受体拮抗剂DMPX可降低苍白球的葡萄糖利用率，同时增加耳蜗核的能量代谢。腺苷A1受体拮抗剂DPCPX可降低苍白球和齿状回的葡萄糖利用率，并增加六个区域（主要是下丘脑、丘脑区域和耳蜗核）的能量代谢率。腺苷A1和A2受体激动剂的脑代谢后果与相应腺苷受体的定位之间存在不匹配。腺苷A2受体激动剂和拮抗剂的代谢作用与该类型受体在运动控制中的已知作用及其对海马和大脑皮层神经元放电的影响一致。腺苷A1受体激动剂的作用非常分散，主要与药物引起的血压短暂下降有关。腺苷A1受体拮抗剂引起的边缘区域葡萄糖利用率增加可能与腺苷对觉醒和心肺功能的调节有关。这些结果与先前用其他方法显示的腺苷系统的神经调节功能高度一致。
