Repagermanium attenuates H<sub>2</sub>S-induced acceleration of Ca<sub>v</sub>3.2 T-type calcium channel activity and pain sensitivity by directly interacting with H<sub>2</sub>S

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  • RepagermaniumはH<sub>2</sub>Sと直接反応することでH<sub>2</sub>Sにより誘起されるCa<sub>v</sub>3.2 T型カルシウムチャネル活性および痛み感受性の増大を抑制する

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<p>Repagermanium, once hydrolyzed into THGP (3-(trihydroxygermyl)propanoic acid) in an aqueous solution, exhibits various biological activities and attenuates osteoporosis, pain, inflammation, etc., although the underlying molecular mechanisms remain unclear. The present study was conducted to see whether THGP would directly interact with H2S, a gasotransmitter, generated by some enzymes including cystathionine-γ-lyase (CSE), which promotes pain sensation by increasing Cav3.2 T-type calcium channel (T-channel) activity. 1H-NMR and LC-MS/MS spectrum analyses indicated that THGP reacts with SH- derived from H2S donors, NaSH or Na2S, generating a sulfur-containing compound. In Cav3.2-transfected HEK293 cells, THGP abolished Na2S-induced enhancement of T-currents. In mice, THGP suppressed the mechanical allodynia caused by intraplantar Na2S or burn injury, as assessed by von Frey test, as did a T-channel blocker and CSE inhibitor. Western blotting demonstrated the burn injury-induced upregulation of CSE protein in the plantar skin. These data suggest that THGP directly interacts with H2S, thereby attenuating H2S-dependent enhancement of Cav3.2 activity and pain sensitivity. The burn injury-induced allodynia is considered to involve the CSE upregulation followed by acceleration of the H2S/Cav3.2 pathway.</p>

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