Skip to main content
SpringerLink
Log in

Ion Channels as Targets for Plant-Derived Drugs

  • Chapter
  • First Online:
Lessons on Caffeine, Cannabis & Co

Part of the book series: Learning Materials in Biosciences ((LMB))

Abstract

Gated ion channels open or close in response to changes in membrane potential, binding of ligands at extracellular or intracellular sites, or mechanical stimuli. Many natural products including plant-derived drugs and plant and animal toxins interfere with the function of ion channels. Here we first discuss neurotoxin binding to voltage-gated ion channels. Nicotine is an agonist for the nicotinic acetylcholine receptor (NAchR). Moreover, many drugs including thujone and synthetic drugs, such as benzamidines, bind to GABA receptors, whereas strychnine antagonizes glycine receptors, e.g. such which mediate feedback signals after muscle contraction. We describe the three isoforms of glutamate receptors and the action of some psychoactive compounds, e.g. ketamine and PCP. Finally, TRPV receptors are briefly touched in connection with their sensing of heat, inflammatory cytokines and the action of capsaicin. In contrast, TRPM8 is described as a cold sensor activated by menthol and related compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Berridge MJ (2012) Calcium signalling remodelling and disease. Biochem Soc Trans 40:297–309

    Article  CAS  Google Scholar 

  • Bormann J (2000) The ‘ABC’ of GABA receptors. Trends Pharmacol Sci 21:16–19

    Article  CAS  Google Scholar 

  • Brams M, Pandya A, Kuzmin D, van Elk R, Krijnen L, Yakel JL, Tsetlin V, Smit AB, Ulens C (2011) A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors. PLoS Biol 9:e1001034

    Article  CAS  Google Scholar 

  • Brito R, Sheth S, Mukherjea D, Rybak LP, Ramkumar V (2014) TRPV1: a potential drug target for treating various diseases. Cell 3:517–545

    Article  CAS  Google Scholar 

  • Cestele S, Catterall WA (2000) Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82:883–892

    Article  CAS  Google Scholar 

  • Cioffi CL (2013) Modulation of NMDA receptor function as a treatment for schizophrenia. Bioorg Med Chem Lett 23:5034–5044

    Article  CAS  Google Scholar 

  • Daly JW (2005) Nicotinic agonists, antagonists, and modulators from natural sources. Cell Mol Neurobiol 25:513–552

    Article  CAS  Google Scholar 

  • Hayashi T (1954) effects of sodium glutamate on the nervous system. Keio J Med 3(4):183–192

    Article  Google Scholar 

  • Hold KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE (2000) Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification. Proc Natl Acad Sci U S A 97:3826–3831

    Article  CAS  Google Scholar 

  • Johnston GA (2014) Muscimol as an ionotropic GABA receptor agonist. Neurochem Res 39:1942–1947

    Article  CAS  Google Scholar 

  • Krienitz L, Ballot A, Kotut K, Wiegand C, Putz S, Metcalf JS, Codd GA, Pflugmacher S (2003) Contribution of hot spring cyanobacteria to the mysterious deaths of Lesser Flamingos at Lake Bogoria, Kenya. FEMS Microbiol Ecol 43:141–148

    Article  CAS  Google Scholar 

  • Li D, He L (2007) Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: a HuGE review and meta-analysis. Genet Med 9:4–8

    Article  CAS  Google Scholar 

  • Luger D, Poli G, Wieder M, Stadler M, Ke S, Ernst M, Hohaus A, Linder T, Seidel T, Langer T, Khom S, Hering S (2015) Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis. Br J Pharmacol 172:5403–5413

    Article  CAS  Google Scholar 

  • Lynagh T, Pless SA (2014) Principles of agonist recognition in Cys-loop receptors. Front Physiol 5:160

    Article  Google Scholar 

  • Noguchi T, Jeon JK, Arakawa O, Sugita H, Deguchi Y, Shida Y, Hashimoto K (1986) Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus. J Biochem 99:311–314

    Article  CAS  Google Scholar 

  • Nys M, Kesters D, Ulens C (2013) Structural insights into Cys-loop receptor function and ligand recognition. Biochem Pharmacol 86:1042–1053

    Article  CAS  Google Scholar 

  • Olsen RW (2015) Allosteric ligands and their binding sites define gamma-aminobutyric acid (GABA) type A receptor subtypes. Adv Pharmacol 73:167–202

    Article  CAS  Google Scholar 

  • Proudfoot A (2006) The early toxicology of physostigmine: a tale of beans, great men and egos. Toxicol Rev 25:99–138

    Article  CAS  Google Scholar 

  • Sigel E, Steinmann ME (2012) Structure, function, and modulation of GABA(A) receptors. J Biol Chem 287:40224–40231

    Article  CAS  Google Scholar 

  • Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, Stevens JT, Weiner ML (2002) Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology 171:3–59

    Article  CAS  Google Scholar 

  • Tilley DC, Eum KS, Fletcher-Taylor S, Austin DC, Dupre C, Patron LA, Garcia RL, Lam K, Yarov-Yarovoy V, Cohen BE, Sack JT (2014) Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells. Proc Natl Acad Sci U S A 111:E4789–E4796

    Article  CAS  Google Scholar 

  • Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62:405–496

    Article  CAS  Google Scholar 

  • Trudell JR, Messing RO, Mayfield J, Harris RA (2014) Alcohol dependence: molecular and behavioral evidence. Trends Pharmacol Sci 35:317–323

    Article  CAS  Google Scholar 

  • Tsavaler L, Shapero MH, Morkowski S, Laus R (2001) Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61:3760–3769

    CAS  PubMed  Google Scholar 

  • Vais H, Atkinson S, Eldursi N, Devonshire AL, Williamson MS, Usherwood PN (2000) A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides. FEBS Lett 470:135–138

    Article  CAS  Google Scholar 

  • Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C (2014) Cytisine versus nicotine for smoking cessation. N Engl J Med 371:2353–2362

    Article  Google Scholar 

  • Watkins SM, Reich A, Fleming LE, Hammond R (2008) Neurotoxic shellfish poisoning. Mar Drugs 6:431–455

    Article  CAS  Google Scholar 

  • Yudin Y, Rohacs T (2012) Regulation of TRPM8 channel activity. Mol Cell Endocrinol 353:68–74

    Article  CAS  Google Scholar 

  • Zhang G, Lin RL, Wiggers M, Snow DM, Lee LY (2008a) Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J Physiol 586:5771–5786

    Article  CAS  Google Scholar 

  • Zhang P, Gao W, Zhang L, Chen L, Shen Q, Wang X, Cui Y (2008b) In vitro evaluation of topical microemulsion of capsaicin free of surfactant. Biol Pharm Bull 31:2316–2320

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department Biology II, LMU Munich, Planegg-Martinsried, Germany

    Angelika Böttger

  2. IZMB-Plant Cell Biology, University of Bonn, Bonn, Germany

    Ute Vothknecht

  3. Department Biology I, LMU Munich, Planegg-Martinsried, Germany

    Cordelia Bolle

  4. Inst. Molecular Toxicology/Pharmacology, Helmholtz Zentrum Münich, Neuherberg, Germany

    Alexander Wolf

Authors
  1. Angelika Böttger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ute Vothknecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cordelia Bolle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angelika Böttger .

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Böttger, A., Vothknecht, U., Bolle, C., Wolf, A. (2018). Ion Channels as Targets for Plant-Derived Drugs. In: Lessons on Caffeine, Cannabis & Co. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-319-99546-5_6

Download citation

Publish with us

Policies and ethics

Search

Navigation