Comparative aspects of nitrobenzylthioinosine and dipyridamole inhibition of adenosine accumulation in rat and guinea pig synaptoneurosomes |
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Institution: | 1. Molecular PathoBiology, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada;2. National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, 1015 Arlington St., Winnipeg, MB R3E 3M4, Canada;3. Viral Diseases Division, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada;4. Mass Spectrometry and Proteomics Core Facility, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada;5. Thermo Fisher Scientific, San Jose, CA, USA;6. Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, 730 William Ave., Winnipeg, MB R3E 0W3, Canada;1. Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100871, China;2. Beijing Engineering Research Center of City Heat, Beijing 100871, China |
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Abstract: | 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 μM 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 IC50 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 3H]adenosine accumulation were also noted. DPR was more potent in inhibiting 3H]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 3H]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. |
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