Effects on transmitter uptake and their cellular and molecular basis

Part of the Milestones in Drug Therapy MDT book series (MDT)


PC12 Cell Hypericum Perforatum Serotonin Uptake Flufenamic Acid Neurotransmitter Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Suzuki O, Katsumata Y, Oya M, Bladt S, Wagner H (1984) Inhibition of monoamine oxidase by hypericin. Planta Med 50: 272–274PubMedGoogle Scholar
  2. 2.
    Bladt S, Wagner H (1994) Inhibition of MAO by fractions and constituents of Hypericum extract. J Geriatr Psychiatry Neurol 7(1): S57–59PubMedGoogle Scholar
  3. 3.
    Thiede HM, Walper A (1994) Inhibition of MAO and COMT by Hypericum extracts and hypericin. J Geriatr Psychiatry Neurol 7(1): S54–S56PubMedGoogle Scholar
  4. 4.
    Reuter HD (1993) Hypericum als pflanzliches Antidepressivum. Zeitschrift für Phytotherapie 14: 239–254Google Scholar
  5. 5.
    Demisch L, Hölzl J, Gollnik B, Kaczmarczyk P (1989) Identification of selective MAO-Type A inhibitors in Hypericum perforatum L. (Hyperforat). Pharmacopsychiatry 22: 194Google Scholar
  6. 6.
    Cott JM (1997) In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry 30: 108–112Google Scholar
  7. 7.
    Müller WE, Rolli M, Schäfer C, Hafner U (1997) Effects of Hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 30: 102–107PubMedGoogle Scholar
  8. 8.
    Neary JT, Whittemore SR, Bu Y, Mehta H, Shi YF (2001) Biochemical mechanisms of action of Hypericum LI160 in glial and neuronal cells: inhibition of neurotransmitter uptake and stimulation of extracellular signal regulated protein kinase. Pharmacopsychiatry 34: S103–107CrossRefPubMedGoogle Scholar
  9. 9.
    Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998) Hyperforin as a possible antidepressant component of Hypericum extracts. Life Sci 63: 499–510CrossRefPubMedGoogle Scholar
  10. 10.
    Gobbi M, Valle FD, Ciapparelli C, Diomede L, Morazzoni P, Verotta L, Caccia S, Cervo L, Mennini T (1999) Hypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 360: 262–269CrossRefPubMedGoogle Scholar
  11. 11.
    Jensen AG, Hansen SH, Nielsen EO (2001) Adhyperforin as a contributor to the effects of Hypericum perforatum L. in biochemical models of antidepressant activity. Life Sci 68: 1593–1605CrossRefPubMedGoogle Scholar
  12. 12.
    Serdarevic N, Eckert GP, Müller WE (2001) The effects of extracts from St. John’s Wort and Kava Kava on brain neurotransmitter levels in the mouse. Pharmacopsychiatry 34: 134–136CrossRefGoogle Scholar
  13. 13.
    Rommelspacher H, Siemanowitz B, Mannel M (2001) Acute and chronic actions of a dry methanolic extract of Hypericum perforatum and a hyperforin-rich extract on dopaminergic and serotoninergic neurones in rat nucleus accumbens. Pharmacopsychiatry 34: 119–126CrossRefPubMedGoogle Scholar
  14. 14.
    Phillipu A (2001) In vivo neurotransmitter release in the loceus coereleus — effects of hyperforin, inescapable shock and fear. Pharmacopsychiatry 34: S111–115CrossRefPubMedGoogle Scholar
  15. 15.
    Calapai G, Crupi A, Firenzuali F, Inferrera G, Squadrito F, Parisi A (2001) Serotonin, norepinephrine and dopamine involvement in the antidepressant action of Hypericum perforatum. Pharmacopsychiatry 34: 45–49CrossRefPubMedGoogle Scholar
  16. 16.
    Teufel-Mayer R, Gleitz J (1997) Effects of long-term administration of Hypericum extracts on the affinity and density of central serotonergic 5HT-1 A and 5HT-2 A receptors. Pharmacopsychiatry 30(2): 113–116Google Scholar
  17. 17.
    Chen F, Rezvani AH, Lawrence AJ (2003) Autoradiographic quantification of neurochemical markers of serotonin, dopamine and opioid systems in rat brain mesolimbic regions following chronic St. John’s Wort treatment. Naunyn-Schmiedeberg’s Arch Pharmacol 367: 126–133Google Scholar
  18. 18.
    Brockmoller J, Reum T, Bauer S, Kerb R, Hubner WD, Roots I (1997) Hypericin and pseudohy-pericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 30(Suppl 2): 94–101PubMedGoogle Scholar
  19. 19.
    Müller WE, Schäfer C (1996) Johanniskraut. In vitro-Studie über Hypericum Extrakt, Hypericin und Kämperol als Antidepressiva. Dtsch Apoth Ztg 136: 1015–1022Google Scholar
  20. 20.
    Rolli M, Schäfer C, Müller WE (1995) Effect of Hypericum extract on neurotransmitter receptor binding and synaptosomal uptake systems. Pharmacopsychiatry 28: 207Google Scholar
  21. 21.
    Misane I, Ogren SO (2001) Effects of Hypericum perforatum (St. John’s Wort) on passive avoidance in the rat: evaluation of potential neurochemical mechanisms underlying its antidepressant activity. Pharmacopsychiatry 34(Suppl 1): S89–97PubMedGoogle Scholar
  22. 22.
    Singer A, Wonnemann M, Müller WE (1999) Hyperforin, a major antidepressant constituent of St. John’s Wort, inhibits serotonin uptake by elevating free intracellular Na+. J Pharmacol Exp Ther 290: 1363–1368PubMedGoogle Scholar
  23. 23.
    Wonnemann M, Singer A, Siebert B, Muller WE (2001) Evaluation of synaptosomal uptake inhibition of the most relevant constituents of St. John’s Wort. Pharmacopsychiatry 34: S148–152PubMedGoogle Scholar
  24. 24.
    Giros B, Caron MG (1993) Molecular characterization of the dopamine transporter. Trends Pharmacol Sci 14: 43–49PubMedGoogle Scholar
  25. 25.
    Kanner BI, Danbolt N, Pines G, Koepsell H, Seeberg E, Mathisen JS (1993) Structure and function of the sodium and potassium-coupled glutamate transporter from rat brain. Biochem Soc Trans 21: 59–61PubMedGoogle Scholar
  26. 26.
    Treiber K, Singer A, Henke B, Müller WE (2004) Hyperforin is a specific activator of non-selective cation channels. Brit J Pharmacol; in pressGoogle Scholar
  27. 27.
    Buchholzer ML, Dovrak C, Chatterjee S, Klein J (2002) Dual modulation of striatal acetylcholine release by hyperforin, a constituent of St. John’s Wort. JPET 301: 1–6Google Scholar
  28. 28.
    Wonnemann M, Singer A, Müller WE (2000) Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by hyperforin, a major constituent of St. John’s Wort. The role of amiloride sensitive sodium conductive pathways. Neuropsychopharmacology 23: 188–197CrossRefPubMedGoogle Scholar
  29. 29.
    Stamouli V, Vakirtzi-Lemonias C, Siffert W (1993) Thrombin and NaF, but not epinephrine, raise cytosolic free Na+ in human platelets. Biochim Biophys Acta 1176: 215–221PubMedGoogle Scholar
  30. 30.
    Reichardt LF, Kelly RB (1983) A molecular description of nerve terminal function. Annu Rev Biochem 52: 871–926PubMedGoogle Scholar
  31. 31.
    Tesfai Y, Brereton HM, Barritt GJ (2001) A diacylglycerol-activated Ca2+ channel in PC12 cells (an adrenal chromaffin cell line) correlates with the expression on TRP-6 (transient receptor potential) protein. Biochem J 358: 717–726PubMedGoogle Scholar
  32. 32.
    Merritt JE, Armstrong WP, Benham CD (1990) SKandF 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem J 271: 515–552PubMedGoogle Scholar
  33. 33.
    Goegelein H, Dahlem D, Englert HC, Lang HJ (1990) Flufenamic acid, mefenamic acid and niflumic acid inhibit single non-selective cation channels in the rat exocrine pancreas. FEBS Lett 268: 79–82PubMedGoogle Scholar
  34. 34.
    Kawanabe Y, Hashimoto N, Masaki T (2002) Characterisation of G proteins involved in activation of nonselective cation channels by endothelin (B) receptor. Br J Pharmacol 136: 1015–1022PubMedGoogle Scholar
  35. 35.
    Krautwurst D, Seifert R, Hescheler J, Schultz G (1992) Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. Biochem J 288 (Pt 3): 1025–1035PubMedGoogle Scholar
  36. 36.
    Miwa S, Iwamuro Y, Zhang XF, Kawanabe Y, Masaki T (2000) LOE 908: a specific blocker of non-selective cation channel. Cardiovasc Drug Rev 18: 61–72Google Scholar
  37. 37.
    Jung S, Mühle A, Schaefer M, Strotmann R, Schultz G, Plant TD (2003) Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth. J Biol Chem 278(6): 3562–3571PubMedGoogle Scholar
  38. 38.
    Clapham DE (2003) TRP channels as cellular sensors. Nature 426: 517–524PubMedGoogle Scholar
  39. 39.
    Inoue R, Okada T, Onoue Y, Hara Y, Shimizu S, Naitoh S, Ito Y, Mori Y (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular α1-adrenoceptor-activated Ca2+-permeable cation channel. Circ Res 88: 325–332PubMedGoogle Scholar
  40. 40.
    Suzuki M, Murata M, Ikeda M, Miyoshi T, Imai M (1998) Primary structure and functional expression of a novel non-selective cation channel. Biochem Biophys Res Commun 242: 191–196PubMedGoogle Scholar
  41. 41.
    Liu RJ, van den Pol AN, Aghajanian GK (2002) Hypocretins (Orexin) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. J Neurosci 22: 9453–9464PubMedGoogle Scholar
  42. 42.
    Clapham DE (2003) TRP channels as cellular sensors. Nature 426: 517–524PubMedGoogle Scholar
  43. 43.
    Eckert GP, Müller WE (2001) Effects of hyperforin on the fluidity of brain membranes. Pharmacopsychiatry 34(Suppl 1): S22–25PubMedGoogle Scholar
  44. 44.
    Wood EG, Eckert GP, Igbavboa U, Müller WE (2003) Amyloid beta-protein interactions with membranes and cholesterol: causes or causality for Alzheimer’s disease. Biochim Biophys Acta 1610: 281–290PubMedGoogle Scholar
  45. 45.
    Ropero S, Chiloeches A, Montes A, Toro-Nozal MJ (2003) Cholesterol cell content modulates GTPase activity of G-proteins in GH4C1 cell membranes. Cell Signall 15: 131–138Google Scholar
  46. 46.
    Keller JH, Karas M, Müller WE, Volmer DA, Eckert GP, Tawab MA, Blume HH, Dingermann T, Schubert-Zsilavecz M (2003) Determination of hyperforin in mouse brain by high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 75: 6084–6088PubMedGoogle Scholar
  47. 47.
    Eckert GP, Keller JH, Jourdan C, Karras M, Volmer DA, Schubert-Zsilavecz M, Müller WE (2004) Hyperforin modifies neuronal membrane properties in vivo. Neurosci Lett 367: 139–143PubMedGoogle Scholar
  48. 48.
    Roz N, Rehavi M (2003) Hyperforin inhibits vesicular uptake of monoamines by dissipating pH gradient across synaptic vesicle membrane. Life Sci 73: 461–470PubMedGoogle Scholar
  49. 49.
    Froestl B, Steiner B, Müller WE (2003) Enhancement of proteolytic processing of the β-amyloid precursor protein by hyperforin. Biochem Pharmacol 66: 2177–2184PubMedGoogle Scholar
  50. 50.
    Klusa V, Germane S, Noldner M, Chatterjee SS (2001) Hypericum extract and hyperforin: memory-enhancing properties in rodents. Pharmacopsychiatry 34: S61–69PubMedGoogle Scholar
  51. 51.
    Holoubek G, Nöldner M, Müller WE (2001) Possible relationship between behavioral and biochemical changes following antidepressant activity. Soc Neurosci, Abstr. 572.14Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2005

Authors and Affiliations

  1. 1.Pharmakologisches Institut für NaturwissenschaftlerBiozentrum Universität FrankfurtFrankfurtGermany

Personalised recommendations