Inhibition of endothelial cell Ca2+ entry and transient receptor potential channels by Sigma‐1 receptor ligands

摘要: Background and Purpose The Sigma-1 receptor (Sig1R) impacts on calcium ion signalling has a plethora of ligands. This study investigated Sig1R its ligands in relation to endogenous events endothelial cells transient potential (TRP) channels. Experimental Approach Intracellular patch clamp measurements were made from human saphenous vein HEK 293 expressing exogenous TRPC5, TRPM2 or TRPM3. applied short interfering RNA was used deplete Sig1R. TRP channels tagged with fluorescent proteins for subcellular localization studies. Key Results In cells, 10–100 μM the antagonist BD1063 inhibited sustained but not responses evoked by histamine. The agonist 4-IBP related BD1047 also inhibitory. SKF10047 had no effect. Sustained entry VEGF hydrogen peroxide BD1063, 4-IBP, SKF10047. TRPC5 TRPM3, TRPM2. Inhibitory effects rapid onset readily reversed washout. TRPM3 Depletion did prevent inhibitory actions co-localize TRPM3. Conclusions Implications The data suggest that two types ligand (BD1047/BD1063 4-IBP) are inhibitors receptor- chemically activated channels, acting relatively directly independently Chemical foundations channel suggested.