SYNTHETIC PEPTIDE FRAGMENTS OF THE TOXIN WTX REDUCE BLOOD PRESSURE IN RATS UNDER GENERAL ANESTHESIA

M. S. Severyukhina; Северюхина М. С.; A. M. Ismailova; Исмаилова А. М.; E. R. Shaykhutdinova; Шайхутдинова Э. Р.; I. A. Dyachenko; Дьяченко И. А.; N. S. Egorova; Егорова Н. С.; A. N. Murashev; Мурашев А. Н.; V. I. Tsetlin; Цетлин В. И.; Yu. N. Utkin; Уткин Ю. Н.

doi:10.31857/S2686738923600516

SYNTHETIC PEPTIDE FRAGMENTS OF THE TOXIN WTX REDUCE BLOOD PRESSURE IN RATS UNDER GENERAL ANESTHESIA

作者: Severyukhina M.S.¹^,2, Ismailova A.M.¹, Shaykhutdinova E.R.¹, Dyachenko I.A.¹, Egorova N.S.³, Murashev A.N.¹, Tsetlin V.I.³, Utkin Y.N.³
隶属关系:
1. Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS
2. Pushchino State Natural-Science Institute
3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
期: 卷 513, 编号 1 (2023)
页面: 575-580
栏目: Articles
URL: https://vestnik.nvsu.ru/2686-7389/article/view/651058
DOI: https://doi.org/10.31857/S2686738923600516
EDN: https://elibrary.ru/GTLMJI
ID: 651058

如何引用文章

全文:

开放存取

##reader.subscriptionAccessGranted##
受限制的访问

订阅存取

详细

Previously, it was shown that the non-conventional toxin WTX from the venom of the cobra Naja kaouthia, when administered intravenously, caused a decrease in blood pressure (BP) and an increase in heart rate (HR) in rats (Ogay et al., 2005). To identify the site of the toxin molecule responsible for these effects, we studied the influence of synthetic peptide fragments of the WTX on BP and HR in normotensive male Sprague Dawley rats under general anesthesia induced by Telazol and Xylazine. It was found that peptides corresponding to the WTX central polypeptide loop, stabilized by a disulfide bond, at intravenous injection at concentrations from 0.1 to 1.0 mg/ml caused a dose-dependent decrease in BP, the HR increasing only in the first 5–10 minutes after administration. Thus, WTX fragments corresponding to the central polypeptide loop reproduce the decrease in blood pressure caused by the toxin.

关键词

non-conventional toxin, WTX, blood pressure, heart rate

参考

Kessler P., Marchot P., Silva M., et al. The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions. // J. Neurochem. 2017. V. 142. Suppl. 2. P. 7–18.
Nirthanan S. Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine. // Biochem. Pharmacol. 2020. V. 181. P. 114168.
Utkin Y.N., Kukhtina V.V., Kryukova E.V., et al. “Weak toxin” from Naja kaouthia is a nontoxic antagonist of alpha 7 and muscle-type nicotinic acetylcholine receptors. // J. Biol. Chem. 2001. V. 276. № 19. P. 15810–15815.
Nirthanan S., Gopalakrishnakone P., Gwee M.C., et al. Non-conventional toxins from Elapid venoms. Toxicon. 2003. V. 41. № 4. P. 397–407.
Mordvintsev D.Y., Polyak Y.L., Rodionov D.I., et al. Weak toxin WTX from Naja kaouthia cobra venom interacts with both nicotinic and muscarinic acetylcholine receptors. FEBS J. 2009. V 276. № 18. P. 5065–5075.
Janssen B.J., Leenders P.J., Smits J.F. Short-term and long-term blood pressure and heart rate variability in the mouse. // Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000. V. 278. № 1. P. R215–R225.
Lyukmanova E.N., Shulepko M.A., Shenkarev Z.O., et al. Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors. Toxicon. 2016. V. 119. P. 274–279.
Shenkarev Z.O., Chesnokov Y.M., Zaigraev M.M., et al. Membrane-mediated interaction of non-conventional snake three-finger toxins with nicotinic acetylcholine receptors. Commun. Biol. 2022. V. 5. №1. P. 1344.
Fruchart-Gaillard C., Gilquin B., Antil-Delbeke S., et al. Experimentally based model of a complex between a snake toxin and the alpha 7 nicotinic receptor. Proc. Natl. Acad. Sci. U S A. 2002. V. 99. № 5. P. 3216–3221.
Nys M., Zarkadas E., Brams M., et al. The molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors. Nat. Commun. 2022. V. 13. № 1. P. 4543.
Lyukmanova E.N., Shenkarev Z.O., Shulepko M.A., et al. Structural Insight into Specificity of Interactions between Nonconventional Three-finger Weak Toxin from Naja kaouthia (WTX) and Muscarinic Acetylcholine Receptors. J. Biol. Chem. 2015. V. 290. № 39. P. 23616–23630.
Marquer C., Fruchart-Gaillard C., Letellier G., et al. Structural model of ligand-G protein-coupled receptor (GPCR) complex based on experimental double mutant cycle data: MT7 snake toxin bound to dimeric hM1 muscarinic receptor. // J. Biol. Chem. 2011. V. 286. № 36. P. 31661–31675.
Ogay A.Y., Rzhevsky D.I., Murashev A.N., et al. Weak neurotoxin from Naja kaouthia cobra venom affects haemodynamic regulation by acting on acetylcholine receptors. // Toxicon. 2005. V. 45. № 1. P. 939–939.
Juillerat M.A., Schwendimann B., Hauert J., et al. Specific binding to isolated acetylcholine receptor of a synthetic peptide duplicating the sequence of the presumed active center of a lethal toxin from snake venom. // J. Biol. Chem. 1982. V. 257. № 6. P. 2901–2907.
Mineev K.S., Kryukova E.V., Kasheverov I.E., et al. Spatial Structure and Activity of Synthetic Fragments of Lynx1 and of Nicotinic Receptor Loop C Models. // Biomolecules. 2020. V. 11. № 1. P. 1.
Шаманаев А.Ю., Алиев О.И., Анищенко А.М., и др. Показатели сердечной деятельности у крыс линии SHR до и после установления стабильно высокого артериального давления // Международный журнал прикладных и фундаментальных исследований. 2016. № 4–6. С. 1115–1118.
Кадомцев Д.В., Пасечникова Е.А., Голубев В.Г. Золетил-ксилазиновый наркоз в экспериментах у крыс // Международный журнал прикладных и фундаментальных исследований. 2015. № 5–1. С. 56–57.
Haass M., Kübler W. Nicotine and sympathetic neurotransmission. // Cardiovasc. Drugs Ther. 1997. V. 10. № 6. P. 657–665.
Muntzel M.S., Abe A., Petersen J.S. Effects of adrenergic, cholinergic and ganglionic blockade on acute depressor responses to metformin in spontaneously hypertensive rats. // J. Pharmacol. Exp. Ther. 1997. V. 281. № 2. P. 618–623.
Holte H.R., Bjørnstad-Ostensen A., Berg T. The role of endogenous bradykinin in blood pressure homeostasis in spontaneously hypertensive rats. // Br. J. Pharmacol. 1996. V. 118. № 8. P. 1925–1930.
Sharma J.N., Amrah S.S., Noor A.R.. Suppression of hypotensive responses of captopril and enalapril by the kallikrein inhibitor aprotinin in spontaneously hypertensive rats. // Pharmacology. 1995. V. 50. № 6. P. 363–369.