PMID- 24189292 OWN - NLM STAT- MEDLINE DCOM- 20140819 LR - 20131230 IS - 1879-3150 (Electronic) IS - 0041-0101 (Linking) VI - 77 DP - 2014 Jan TI - Vietnamese Heterometrus laoticus scorpion venom: evidence for analgesic and anti-inflammatory activity and isolation of new polypeptide toxin acting on Kv1.3 potassium channel. PG - 40-8 LID - S0041-0101(13)00413-3 [pii] LID - 10.1016/j.toxicon.2013.10.027 [doi] AB - The scorpion Heterometrus laoticus (Scorpionidae) inhabits Indochinese peninsula and is widely distributed in South-West Vietnam. Since no human fatalities caused by H. laoticus stings were reported, no systematic characterization of the venom was earlier done. In this study we report on biological activity of the venom from H. laoticus caught in Vietnamese province An Giang. The venom manifested a very low acute toxicity with LD50 of about 190 mg/kg body weight in mice at subcutaneous (s.c.) injection and 12 mg/kg at intravenous injection. The venom analgesic effects using tail immersion and writhing tests as well as anti-inflammatory effect using carrageenan test were analyzed at doses of 9.5 and 19 mg/kg at s.c. injections. It was found that at two doses tested H. laoticus venom showed both anti-nociceptive and anti-inflammatory activity. The venom was fractionated by means of gel-filtration and reversed-phase HPLC. As a result several polypeptide toxins were isolated and new toxin hetlaxin was identified. Its amino acid sequence was determined and binding to the extracellular vestibule of the K(+)-conducting pore of Kv1.1 and Kv1.3 potassium channels was studied. Hetlaxin belongs to the scorpion alpha-toxin family and is the first toxin isolated from H. laoticus venom which possesses high affinity (K(i) 59 nM) to Kv1.3 potassium channel. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Hoang, Anh N AU - Hoang AN AD - Institute of Applied Materials Science, Vietnam Academy of Science and Technology, 01 Mac Dinh Chi Street, District 1, Ho Chi Minh, Viet Nam. FAU - Vo, Hoang D M AU - Vo HD AD - Institute of Applied Materials Science, Vietnam Academy of Science and Technology, 01 Mac Dinh Chi Street, District 1, Ho Chi Minh, Viet Nam. FAU - Vo, Nguyen P AU - Vo NP AD - Medical and Pharmaceutical University, 41 Dinh Tien Hoang Street, District 1, Ho Chi Minh, Viet Nam. FAU - Kudryashova, Kseniya S AU - Kudryashova KS AD - Biological Faculty, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Nekrasova, Oksana V AU - Nekrasova OV AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Feofanov, Alexey V AU - Feofanov AV AD - Biological Faculty, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Kirpichnikov, Mikhail P AU - Kirpichnikov MP AD - Biological Faculty, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Andreeva, Tatyana V AU - Andreeva TV AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Serebryakova, Marina V AU - Serebryakova MV AD - Belozersky Institute for Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia. FAU - Tsetlin, Victor I AU - Tsetlin VI AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. FAU - Utkin, Yuri N AU - Utkin YN AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia; OOO Syneuro, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia. Electronic address: utkin@mx.ibch.ru. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131101 PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Analgesics) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Kv1.3 Potassium Channel) RN - 0 (Scorpion Venoms) RN - 0 (hetlaxin, Heterometrus laoticus) SB - IM MH - Amino Acid Sequence MH - Analgesics/*pharmacology MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Chemical Fractionation MH - Chromatography, Reverse-Phase MH - Kv1.3 Potassium Channel/*metabolism MH - Lethal Dose 50 MH - Mice MH - Molecular Sequence Data MH - Scorpion Venoms/genetics/pharmacology/*toxicity MH - Scorpions/*chemistry MH - Sequence Analysis, Protein MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - Statistics, Nonparametric MH - Time Factors MH - Toxicity Tests, Acute MH - Vietnam OTO - NOTNLM OT - Biological activity OT - Heterometrus laoticus OT - Potassium channel OT - Scorpion OT - Toxicity OT - Venom EDAT- 2013/11/06 06:00 MHDA- 2014/08/20 06:00 CRDT- 2013/11/06 06:00 PHST- 2013/06/04 00:00 [received] PHST- 2013/09/14 00:00 [revised] PHST- 2013/10/24 00:00 [accepted] PHST- 2013/11/06 06:00 [entrez] PHST- 2013/11/06 06:00 [pubmed] PHST- 2014/08/20 06:00 [medline] AID - S0041-0101(13)00413-3 [pii] AID - 10.1016/j.toxicon.2013.10.027 [doi] PST - ppublish SO - Toxicon. 2014 Jan;77:40-8. doi: 10.1016/j.toxicon.2013.10.027. Epub 2013 Nov 1.