title: Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells.
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.
authors.affiliation: Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Varga
authors.forename: Georgina
authors.initials: G
authors.lastname: Gurrola-Briones
authors.forename: Ferenc
authors.initials: F
authors.lastname: Papp
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Rodríguez de la Vega
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pedraza-Alva
authors.forename: Rajeev B
authors.initials: RB
authors.lastname: Tajhya
authors.forename: Rezso
authors.initials: R
authors.lastname: Gaspar
authors.forename: Luis
authors.initials: L
authors.lastname: Cardenas
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rosenstein
authors.forename: Christine
authors.initials: C
authors.lastname: Beeton
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Panyi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism; D019556:COS Cells; D020013:Calcium Signaling / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012604:Scorpion Venoms / Q000378:metabolism; D012605:Scorpions / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D051664:Kv1.3 Potassium Channel; D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms