Piezo1 protein, encoded by PIEZO1 gene, is a mechanically-activated ion channel that links mechanical forces to biological signals. Piezo1 contains 36 transmembrane domains and functions as a homotetramer. Piezo1 plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. Moreover, Piezo1 acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation and it plays a key role in blood vessel formation and vascular structure in both development and adult physiology. GlyT2-IN-1, also termed ‘Yoda-1’, is an agonist for both human and mouse Piezo1, with EC50 values of 26.6 μM and 17.1μM for human and mouse Piezo1, respectively[3]. In HEK293T cells transiently transfected with mouse Piezo1, Yoda-1 mediated Ca2+ responses at the concentration of 25 μM, and this effect depended on calcium influx as the chelation of extracellular calcium dramatically reduced the responses and the depletion of intracellular calcium stores did not. Also in mouse Piezo1 transfected HEK293T cells, using a cell attached patch configuration, it was measured that Yoda-1 notably slowed the inactivation phase of the transient currents at the concentration of 30 μM. Utilizing artificial droplet lipid bilayers, it was shown that Yoda-1 activated purified Piezo1 channels in the absence of other cellular components at the concentration of 1 μM[3].
Yoda 1 动物研究
Dose
Mice: 0.4 mg/kg[3] (duct injection, 5 µL/min for 10 min)
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