title: Vietnamese Heterometrus laoticus scorpion venom: evidence for analgesic and anti-inflammatory activity and isolation of new polypeptide toxin acting on Kv1.3 potassium channel.
abstract: 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.
authors.affiliation: Institute of Applied Materials Science, Vietnam Academy of Science and Technology, 01 Mac Dinh Chi Street, District 1, Ho Chi Minh, Viet Nam.
authors.forename: Anh N
authors.initials: AN
authors.lastname: Hoang
authors.affiliation: Institute of Applied Materials Science, Vietnam Academy of Science and Technology, 01 Mac Dinh Chi Street, District 1, Ho Chi Minh, Viet Nam.
authors.forename: Hoang D M
authors.initials: HD
authors.lastname: Vo
authors.affiliation: Medical and Pharmaceutical University, 41 Dinh Tien Hoang Street, District 1, Ho Chi Minh, Viet Nam.
authors.forename: Nguyen P
authors.initials: NP
authors.lastname: Vo
authors.affiliation: 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.
authors.forename: Kseniya S
authors.initials: KS
authors.lastname: Kudryashova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Nekrasova
authors.affiliation: 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.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Feofanov
authors.affiliation: 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.
authors.forename: Mikhail P
authors.initials: MP
authors.lastname: Kirpichnikov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Andreeva
authors.affiliation: Belozersky Institute for Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Serebryakova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Tsetlin
authors.affiliation: 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.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Utkin
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005591:Chemical Fractionation; D056148:Chromatography, Reverse-Phase; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D012604:Scorpion Venoms / Q000235:genetics / Q000494:pharmacology / Q000633:toxicity*; D012605:Scorpions / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric; D013997:Time Factors; D023382:Toxicity Tests, Acute; D014744:Vietnam
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D051664:Kv1.3 Potassium Channel; D012604:Scorpion Venoms; C583668:hetlaxin, Heterometrus laoticus
keywords: Biological activity; Heterometrus laoticus; Potassium channel; Scorpion; Toxicity; Venom