Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons.
Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons.
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作者：
海洋蓝藻是生物活性代谢物的丰富来源，已被用作药物发现的线索和基础科学研究的药理学工具。在这里，我们描述了在三种不同场合从curaao中重新分离出一种众所周知的代谢物barbamide，并描述了barbamide与哺乳动物神经系统靶点的生物相互作用。Barbamide最初是作为一种丝状海洋蓝藻的杀软体剂被发现的。在我们的研究中，我们几乎没有发现对哺乳动物细胞培养物有毒性的证据。然而，当对已知参与伤害感觉和感觉神经元活动的45个受体和转运体进行结合亲和力筛选时，barbamide显示出几种亲和力。我们发现多巴胺转运体、kappa阿片受体和sigma受体（sigma-1和sigma-2也称为跨膜蛋白97；TMEM97）的结合亲和力很高。我们在离体雌性小鼠感觉神经元中测试了barbamide，以探索其对这些细胞中钙通量的功能影响。Barbamide本身对钙通量没有明显的影响。然而，barbamide增强了TRPV1激动剂辣椒素的作用，并增强了细胞内钙耗尽后的储存操作钙进入（SOCE）反应。总的来说，这些结果证明了barbamide在感觉神经元上的生物学潜力，对未来围绕该分子的药物开发项目具有重要意义。
Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.
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Sigma-2受体 /跨膜蛋白97（σ2R / TMEM97）调节剂JVW-1034可减少雄性小鼠的大量饮酒和相关疼痛状态。
影响因子：
4.7
作者：
Quadir SG;Tanino SM;Rohl CD;Sahn JJ;Yao EJ;Cruz LDR;Cottone P;Martin SF;Sabino V
通讯作者：
Sabino V
影响因子：
14.5
作者：
North, Robert Y.;Li, Yan;Dougherty, Patrick M.
通讯作者：
Dougherty, Patrick M.
影响因子：
5.1
作者：
Jiménez, JI;Scheuer, PJ
通讯作者：
Scheuer, PJ
影响因子：
1.3
作者：
Linciano, Pasquale;Rossino, Giacomo;Collina, Simona
通讯作者：
Collina, Simona
DOI：
10.1073/pnas.1715972115
发表时间：
2018-02-13
影响因子：
11.1
作者：
Ortiz-Renteria, Miguel;Juarez-Contreras, Rebeca;Morales-Lazaro, Sara L.
通讯作者：
Morales-Lazaro, Sara L.