Morgan P F, Marangos P J
National Institutes of Health, NIMH, Unit of Neurochemistry, Biological Psychiatry Branch, Building 10, Room 3C-210, Bethesda, MD 20892, U.S.A.
Neurochem Int. 1987;11(3):339-46. doi: 10.1016/0197-0186(87)90055-6.
Dipyridamole (DPR) and nitrobenzylthioinosine (NBI) inhibition of adenosine accumulation in synaptoneurosomes derived from rat cerebral cortex, rat cerebellum, guinea pig cerebral cortex and guinea pig cerebellum was investigated. The inhibition of adenosine accumulation by NBI was observed to be distinctly biphasic in both guinea pig and rat synaptoneurosomes. Such biphasic inhibition consisted of a nM potency component to inhibition, accounting for 20-30% of the maximum inhibition, and a ?M potency component, accounting for the remaining 70-80% maximum inhibition. Such an inhibitory profile contrasts sharply with that of DPR which appears monophasic, with a mean IC(50) of between 10(?7) M and 10(?6) M, in all rat and guinea pig synaptoneurosomes preparations studied. Further differences between the potency of NBI and DPR in inhibiting [(3)H]adenosine accumulation were also noted. DPR was more potent in inhibiting [(3)H]adenosine accumulation in guinea pig cerebellar synaptoneurosomes than in cerebral cortex synaptoneurosomes. In rat synaptoneurosomes, the reverse selectivity was observed. DPR was also 2-6 fold (depending on brain region of comparison) more potent in inhibiting adenosine accumulation in guinea pig synaptoneurosomes than in inhibiting such accumulation in rat synaptoneurosomes. In contrast, NBI was approximately equipotent in inhibiting adenosine accumulation in rat and guinea pig synaptoneurosomes. Additional binding studies using [(3)H]NBI are also reported. The data presented are entirely consistent with the hypotheses that (1) NBI and DPR bind to functionally relevant sites and (2) there are different populations of nucleoside transporters in mammalian brain.
研究了双嘧达莫（DPR）和硝基苄硫基肌苷（NBI）对源自大鼠大脑皮层、大鼠小脑、豚鼠大脑皮层和豚鼠小脑的突触体中腺苷积累的抑制作用。在豚鼠和大鼠的突触体中，均观察到NBI对腺苷积累的抑制作用明显呈双相性。这种双相抑制由一个纳摩尔效力的抑制成分组成，占最大抑制作用的20%-30%，以及一个微摩尔效力的成分，占其余70%-80%的最大抑制作用。这种抑制特征与DPR形成鲜明对比，在所有研究的大鼠和豚鼠突触体制剂中，DPR的抑制作用似乎是单相的，平均半数抑制浓度（IC50）在10^(-7)M至10^(-6)M之间。还注意到NBI和DPR在抑制[³H]腺苷积累的效力方面的进一步差异。DPR在抑制豚鼠小脑突触体中[³H]腺苷积累方面比在大脑皮层突触体中更有效。在大鼠突触体中，观察到相反的选择性。DPR在抑制豚鼠突触体中腺苷积累方面也比抑制大鼠突触体中的积累效力高2-6倍（取决于比较的脑区）。相比之下，NBI在抑制大鼠和豚鼠突触体中腺苷积累方面的效力大致相当。还报告了使用[³H]NBI进行的额外结合研究。所呈现的数据完全符合以下假设：（1）NBI和DPR与功能相关位点结合；（2）哺乳动物大脑中存在不同群体的核苷转运体。
