Polyoxometalates function as indirect activators of a G protein-coupled receptor

Abstract

The luteinizing hormone receptor (LHR), a G protein-coupled receptor (GPCRs), can initiate signaling in the presence of some vanadium-containing compounds as a result of vanadium compound interactions with the membrane lipids and/or the cell membrane lipid interface. The ability of LHR expressed in CHO cells to initiate signaling in the presence of highly charged and water-soluble polyoxovanadates (POV) including Na₃[H₃V₁₀O₂₈] (V₁₀) and two mixed-valence heteropolyoxovanadates, K(NH₄)₄[H₆V₁₄O₃₈(PO₄)]·11H₂O (V₁₄) and [(CH₃)₄N]₆[V₁₅O₃₆(Cl)] (V₁₅), was investigated here. Interactions of the vanadium compounds with CHO cells decreased the packing of membrane lipids, drove aggregation of LHR and increased signal transduction by LHR. Cell responses were comparable to, or in the case of V₁₄ and V₁₅, greater than those seen for cells treated with human chorionic gonadotropin (hCG), a naturally-occurring LHR ligand produced in early pregnancy in humans. POV effects were observed for CHO cells where LHR was expressed at 10 000 or 32 000 LHR per cell but not when LHR was overexpressed with receptor numbers >100 000 LHR per cell. To determine which POV species were present in the cell medium during cell studies, the speciation of vanadate (V₁), V₁₀, V₁₄ or V₁₅ in cell medium was monitored using ⁵¹V NMR and EPR spectroscopies. We found that all the POVs initiated signaling, but V₁₅ and V₁₀ had the greatest effects on cell function, while V₁ was significantly less active. However, because of the complex nature of vanadium compounds speciation, the effects on cell function may be due to vanadium species formed in the cell medium over time.