Planta Med 2008; 74(10): 1235-1239
DOI: 10.1055/s-2008-1081292
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Converging Effects of Ginkgo biloba Extract at the Level of Transmitter Release, NMDA and Sodium Currents and Dendritic Spikes

Bernadett K. Szasz1 , Nora Lenkey1 , Albert M. I. Barth1 , Arpad Mike1 , Zsolt Somogyvari2 , Orsolya Farkas2 , Balazs Lendvai1
  • 1Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
  • 2ASI Budapest, Hungary
Further Information

Publication History

Received: March 3, 2008 Revised: May 20, 2008

Accepted: May 25, 2008

Publication Date:
11 July 2008 (online)

Abstract

In this study, an attempt was made to integrate the effects of Ginkgo biloba extract (GBE) in different experimental systems (in vitro cochlea, brain slice preparations and cortical cell culture) to elucidate whether these processes converge to promote neuroprotection or interfere with normal neural function. GBE increased the release of dopamine in the cochlea. NMDA-evoked currents were dose-dependently inhibited by rapid GBE application in cultured cortical cells. GBE moderately inhibited Na+ channels at depolarised holding potential in cortical cells. These inhibitory effects by GBE may sufficiently contribute to the prevention of excitotoxic damage in neurons. However, these channels also interact with memory formation at the cellular level. The lack of effect by GBE on dendritic spike initiation in neocortical layer 5 pyramidal neurons indicates that the integrative functions may remain intact during the inhibitory actions of GBE.

Abbreviations

bAP:backpropagating action potentials

DA:dopamine

FR:fractional release

GBE:Ginkgo biloba extract

NMDA:N-methyl-d-aspartate

AS:adenine sulfate

References

  • 1 Ahlemeyer B, Krieglstein J. Pharmacological studies supporting the therapeutic use of Ginkgo biloba extract for Alzheimer's disease.  Pharmacopsychiatry. 2003;  36 S8-14
  • 2 Domorakova I, Burda J, Mechirova E, Ferikova M. Mapping of rat hippocampal neurons with NeuN after ischemia/reperfusion and Ginkgo biloba extract (EGb 761) pretreatment.  Cell Mol Neurobiol. 2006;  26 1193-204
  • 3 Luo Y, Smith J V, Paramasivam V, Burdick A, Curry K J, Buford J P. et al . Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.  Proc Natl Acad Sci U S A. 2002;  99 12 197-202
  • 4 Le Bars P L, Katz M M, Berman N, Itil T M, Freedman A M, Schatzberg A F. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.  JAMA. 1997;  278 1327-32
  • 5 Brunetti L, Orlando G, Menghini L, Ferrante C, Chiavaroli A, Vacca M. Ginkgo biloba leaf extract reverses amyloid β-peptide-induced isoprostane production in rat brain in vitro.  Planta Med. 2006;  72 1296-9
  • 6 Clostre F. From the body to the cell membrane: the different levels of pharmacological action of Ginkgo biloba extract.  Presse Med. 1986;  15 1529-38
  • 7 Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extract.  Cell Mol Life Sci. 2003;  60 1779-92
  • 8 Chen B, Cai J, Song L S, Wang X, Chen Z. Effects of Ginkgo biloba extract on cation currents in rat ventricular myocytes.  Life Sci. 2005;  76 1111-21
  • 9 Wu Y, Li S, Cui W, Zu X, Wang F, Du J. Ginkgo biloba extract improves coronary blood flow in patients with coronary artery disease: role of endothelium-dependent vasodilation.  Planta Med. 2007;  73 624-8
  • 10 Chen L, Liu C J, Tang M, Li A, Hu X W, Du Y M. et al . Action of aluminum on high voltage-dependent calcium current and its modulation by ginkgolide B.  Acta Pharmacol Sin. 2005;  26 539-45
  • 11 Xiao Z Y, Sun C K, Xiao X W, Lin Y Z, Li S, Ma H. et al . Effects of Ginkgo biloba extract against excitotoxicity induced by NMDA receptors and mechanism thereof.  Zhonghua Yi Xue Za Zhi. 2006;  86 2479-84
  • 12 Weichel O, Hilgert M, Chatterjee S S, Lehr M, Klein J. Bilobalide, a constituent of Ginkgo biloba, inhibits NMDA-induced phospholipase A2 activation and phospholipid breakdown in rat hippocampus.  Naunyn Schmiedebergs Arch Pharmacol. 1999;  360 609-15
  • 13 Kanada A, Nishimura Y, Yamaguchi J Y, Kobayashi M, Mishima K, Horimoto K. et al . Extract of Ginkgo biloba leaves attenuates kainate-induced increase in intracellular Ca2+ concentration of rat cerebellar granule neurons.  Biol Pharm Bull. 2005;  28 934-6
  • 14 Oestreicher E, Arnold W, Ehrenberger K, Felix D. Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs.  Hear Res. 1997;  107 46-52
  • 15 Ruel J, Nouvian R, Gervais d′Aldin C, Pujol R, Eybalin M, Puel J L. Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea.  Eur J Neurosci. 2001;  14 977-86
  • 16 Liu Y, Wong T P, Aarts M, Rooyakkers A, Liu L, Lai T W. et al . NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo.  J Neurosci. 2007;  27 2846-57
  • 17 Gaborjan A, Lendvai B, Vizi E S. Neurochemical evidence of dopamine release by lateral olivocochlear efferents and its presynaptic modulation in guinea-pig cochlea.  Neuroscience. 1999;  90 131-8
  • 18 Barth A M, Vizi E S, Lendvai B. Noradrenergic enhancement of Ca2+ responses of basal dendrites in layer 5 pyramidal neurons of the prefrontal cortex.  Neurochem Int. 2007;  51 323-7
  • 19 Szabo S I, Zelles T, Vizi E S, Lendvai B. The effect of nicotine on spiking activity and Ca2+ dynamics of dendritic spines in rat CA1 pyramidal neurons.  Hippocampus. 2008;  18 376-85
  • 20 Szasz B K, Mike A, Karoly R, Gerevich Z, Illes P, Vizi E S. et al . Direct inhibitory effect of fluoxetine on N-methyl-D-aspartate receptors in the central nervous system.  Biol Psychiatry. 2007;  62 1303-9
  • 21 Lenkey N, Karoly R, Kiss J P, Szasz B K, Vizi E S, Mike A. The mechanism of activity-dependent sodium channel inhibition by the antidepressants fluoxetine and desipramine.  Mol Pharmacol. 2006;  70 2052-63
  • 22 MacDermott A B, Role L W, Siegelbaum S A. Presynaptic ionotropic receptors and the control of transmitter release.  Annu Rev Neurosci. 1999;  22 443-85
  • 23 Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology.  Curr Opin Pharmacol. 2007;  7 39-47
  • 24 Golding N L, Spruston N. Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons.  Neuron. 1998;  21 1189-200
  • 25 Larkum M E, Kaiser K M, Sakmann B. Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials.  Proc Natl Acad Sci U S A. 1999;  96 14 600-4
  • 26 Barth A M, Vizi E S, Zelles T, Lendvai B. α2-Adrenergic receptors modify dendritic spike generation via HCN channels in the prefrontal cortex.  J Neurophysiol. 2008;  99 394-401
  • 27 Dave J R, Williams A J, Moffett J R, Koenig M L, Tortella F C. Studies on neuronal apoptosis in primary forebrain cultures: neuroprotective/anti-apoptotic action of NR2B NMDA antagonists.  Neurotox Res. 2003;  5 255-64
  • 28 Nikam S S, Meltzer L T. NR2B selective NMDA receptor antagonists.  Curr Pharm Des. 2002;  8 845-55
  • 29 Palmer G C. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.  Curr Drug Targets. 2001;  2 241-71

Balazs Lendvai, MD, PhD

Institute of Experimental Medicine

Hungarian Academy of Sciences

Department of Pharmacology

Budapest 1083

Szigony u. 43

Hungary

Phone: +36/1/299/1001

Fax: +36/1/210/9423

Email: lendvai@koki.hu