Extracellular adenosine triphosphate (ATP) regulates a broad variety of physiological functions in a number of tissues partly via ionotropic P2X receptors. Therefore, P2X receptors are promising targets for the development of therapeutically active molecules. Bile acids are cholesterol-derived amphiphilic molecules; their primary function is the facilitation of efficient nutrient fat digestion. However, bile acids have also been shown to serve as signaling molecules and as modulators of different membrane proteins and receptors including ion channels. In addition, some P2X receptors are sensitive to structurally related steroid hormones. In this study, we systematically analyzed whether rat P2X receptors are affected by micromolar concentrations of different bile acids. The taurine-conjugated bile acids TLCA, THDCA, and TCDCA potently inhibited P2X2, whereas other P2X receptors were only mildly affected. Furthermore, stoichiometry and species origin of the P2X receptors affected the modulation by bile acids: in comparison to rat P2X2, the heteromeric P2X2/3 receptor was less potently modulated and the human P2X2 receptor was potentiated by TLCA. In summary, bile acids are a new class of P2X receptor modulators, which might be of physiological relevance.

中文翻译：

---

胆汁酸是大鼠P2X2受体的有效抑制剂。

细胞外三磷酸腺苷（ATP）部分通过离子型P2X受体调节许多组织中的多种生理功能。因此，P2X受体是治疗活性分子发展的有希望的目标。胆汁酸是胆固醇衍生的两亲分子。它们的主要功能是促进有效的营养脂肪消化。但是，胆汁酸也已显示出可以作为信号分子，并充当不同膜蛋白和受体（包括离子通道）的调节剂。此外，某些P2X受体对与结构相关的类固醇激素敏感。在这项研究中，我们系统地分析了大鼠P2X受体是否受不同胆汁酸微摩尔浓度的影响。牛磺酸结合的胆汁酸TLCA，THDCA，TCDCA和TCDCA有效抑制P2X2，而其他P2X受体仅受到轻微影响。此外，P2X受体的化学计量和物种起源影响胆汁酸的调节：与大鼠P2X2相比，异聚体P2X2 / 3受体的调节作用较弱，而人P2X2受体则由TLCA增强。总之，胆汁酸是一类新的P2X受体调节剂，可能与生理相关。