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Background
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Ugr9-1 (π-AnmTX Ugr 9a-1) was isolated from the venom of the sea anemone Urticina grebelnyi. Ugr 9-1 reversibly inhibits homomeric human ASIC3. Ugr9-1 fully inhibits transient currents with an IC50 value of around 10 μM and also partially blocks sustained currents (IC50 = 1.4 μM). The peculiarity of this peptide is its ability to block ASIC3 when activated at weak pH ( pH 4.0). Ugr 9-1 does not block or activate ASIC1a, ASIC1b, ASIC2a and Kv1.3 at significant concentrations. Ugr 9-1 significantly reverses inflammatory and acid-induced pain in-vivo in mice. The antinociceptive effect is attributed to the block of the sustained inward Na+ current in sensitive neurons. The mode of action of Ugr 9-1 on ASIC3 is supposedly new compared to that of APETx2 or small organic compounds (sevanol or amiloride).
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