Abstract
Blockade of Kv1.3 K(+) channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. Vm24 (α-KTx 23.1) is a novel 36-residue Kv1.3-specific peptide isolated from the venom of the scorpion Vaejovis mexicanus smithi. Vm24 inhibits Kv1.3 channels of human lymphocytes with high affinity (K(d) = 2.9 pM) and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits the proliferation and Ca(2+) signaling of human T cells in vitro and reduces delayed-type hypersensitivity reactions in rats in vivo. Our results indicate that Vm24 has exceptional pharmacological properties that make it an excellent candidate for treatment of certain autoimmune diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / drug therapy
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Autoimmune Diseases / metabolism
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COS Cells
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Calcium Signaling / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Chlorocebus aethiops
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Female
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HEK293 Cells
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Humans
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Immunosuppressive Agents / pharmacology*
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Interleukin-2 Receptor alpha Subunit / metabolism
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Kv1.3 Potassium Channel / antagonists & inhibitors*
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Kv1.3 Potassium Channel / metabolism
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Lymphocyte Activation / drug effects
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Peptides / pharmacology
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Potassium Channel Blockers / pharmacology*
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Rats
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Rats, Inbred Lew
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Scorpion Venoms / metabolism
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Scorpions / metabolism
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T-Lymphocytes / drug effects*
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T-Lymphocytes / metabolism
Substances
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IL2RA protein, human
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Immunosuppressive Agents
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Interleukin-2 Receptor alpha Subunit
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Kv1.3 Potassium Channel
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Peptides
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Potassium Channel Blockers
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Scorpion Venoms