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Method of screening for a drug candidate that increases ATP release from RBCs stimulated via the Gs or Gi pathway
Method of screening for a drug candidate that increases ATP release from RBCs stimulated via the Gs or Gi pathway
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机译:筛选增加通过Gs或Gi途径刺激的RBC中ATP释放的候选药物的方法
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摘要
The invention is based upon the discovery that red blood cells contain phosphodiesterase 3B (PDE3B), and that inhibition of that phosphodiesterase allows for an enhanced accumulation of cAMP and subsequent release of ATP. It was further discovered that RBCs treated with insulin accumulate significantly less cAMP and release significantly less ATP than normal RBCs. Likewise, RBCs of patients suffering from type 2 diabetes (hyperinsulinemia) accumulate significantly less cAMP and release significantly less ATP than normal RBCs. It was further discovered that prostaglandin analogues synergistically work with phosphodiesterase 3B inhibitors to improve or increase cAMP accumulation and ATP release by RBCs. Thus the invention is directed to compositions and methods for improving ATP release by RBCs, via administering PDE3B inhibitor or a combination of PDE3B inhibitor and prostaglandin analogue.
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