Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors

Research output: Contribution to journalJournal article

Standard

Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors. / Ivic, Lidija; Sands, Tristan T J; Fishkin, Nathan; Nakanishi, Koji; Kriegstein, Arnold R; Strømgaard, Kristian.

In: Journal of Biological Chemistry, Vol. 278, No. 49, 05.12.2003, p. 49279-49285.

Research output: Contribution to journalJournal article

Harvard

Ivic, L, Sands, TTJ, Fishkin, N, Nakanishi, K, Kriegstein, AR & Strømgaard, K 2003, 'Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors', Journal of Biological Chemistry, vol. 278, no. 49, pp. 49279-49285. https://doi.org/10.1074/jbc.M304034200

APA

Ivic, L., Sands, T. T. J., Fishkin, N., Nakanishi, K., Kriegstein, A. R., & Strømgaard, K. (2003). Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors. Journal of Biological Chemistry, 278(49), 49279-49285. https://doi.org/10.1074/jbc.M304034200

Vancouver

Ivic L, Sands TTJ, Fishkin N, Nakanishi K, Kriegstein AR, Strømgaard K. Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors. Journal of Biological Chemistry. 2003 Dec 5;278(49):49279-49285. https://doi.org/10.1074/jbc.M304034200

Author

Ivic, Lidija ; Sands, Tristan T J ; Fishkin, Nathan ; Nakanishi, Koji ; Kriegstein, Arnold R ; Strømgaard, Kristian. / Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 49. pp. 49279-49285.

Bibtex

@article{6d5f0a14c7d949c686eedad523ff6148,
title = "Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors",
abstract = "Glycine and gamma-aminobutyric acid, type A (GABA(A)) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA(A) receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA(A) and recombinant glycine alpha-homomeric receptor antagonist.",
keywords = "Animals, Cerebral Cortex, Female, GABA-A Receptor Antagonists, Ginkgo biloba, Lactones, Picrotoxin, Pregnancy, Rats, Rats, Sprague-Dawley, Receptors, Glycine, Terpenes",
author = "Lidija Ivic and Sands, {Tristan T J} and Nathan Fishkin and Koji Nakanishi and Kriegstein, {Arnold R} and Kristian Str{\o}mgaard",
year = "2003",
month = "12",
day = "5",
doi = "10.1074/jbc.M304034200",
language = "English",
volume = "278",
pages = "49279--49285",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "49",

}

RIS

TY - JOUR

T1 - Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors

AU - Ivic, Lidija

AU - Sands, Tristan T J

AU - Fishkin, Nathan

AU - Nakanishi, Koji

AU - Kriegstein, Arnold R

AU - Strømgaard, Kristian

PY - 2003/12/5

Y1 - 2003/12/5

N2 - Glycine and gamma-aminobutyric acid, type A (GABA(A)) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA(A) receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA(A) and recombinant glycine alpha-homomeric receptor antagonist.

AB - Glycine and gamma-aminobutyric acid, type A (GABA(A)) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA(A) receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA(A) and recombinant glycine alpha-homomeric receptor antagonist.

KW - Animals

KW - Cerebral Cortex

KW - Female

KW - GABA-A Receptor Antagonists

KW - Ginkgo biloba

KW - Lactones

KW - Picrotoxin

KW - Pregnancy

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Glycine

KW - Terpenes

U2 - 10.1074/jbc.M304034200

DO - 10.1074/jbc.M304034200

M3 - Journal article

C2 - 14504293

VL - 278

SP - 49279

EP - 49285

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 49

ER -

ID: 45810094