当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Inhibitory effects of oenanthotoxin analogues on GABAergic currents in cultured rat hippocampal neurons depend on the polyacetylenes' polarity.

Inhibitory effects of oenanthotoxin analogues on GABAergic currents in cultured rat hippocampal neurons depend on the polyacetylenes' polarity.

Abstract：

:Oenanthotoxin (OETX) and dihydro-OETX are polyacetylenic diols occurring in Oenanthe crocata and are known to exert proconvulsant effects. We have recently demonstrated that these compounds downregulated GABAergic currents (Appendino et al., 2009) and that OETX induced open channel block and allosterically modulated GABA(A) receptors (Wyrembek et al., 2010). O. crocata also contains several minor OETX analogues and in the present study we tested whether their effect on GABA(A) receptors depends on the compounds' polarity. We investigated a series of five polyacetylenes characterized by a higher lipophylicity than OETX, (1-acetyl-2,3-dihydrooenanthotoxin - X1, 14-acetyloenanthotoxin-X2, 1-deoxyoenanthotoxin - X3, 14-deoxyoenanthotoxin - X4, 14-dehydro-1-deoxyOETX - X5, polarity sequence: X1>X2>X3>X4>X5). Their effects were tested first on miniature inhibitory postsynaptic currents (mIPSCs). All but X3, significantly decreased the mIPSC amplitudes while X1, X2, X4 decreased, and X3 and X5 increased the mIPSC frequency. The lack of a clear correlation between the compounds' polarity and their effect on mIPSCs might result from their presynaptic effects. We thus considered their impact on current responses to exogenous GABA applications. Amplitude reduction of current responses was most prominent for X1 and virtually absent for X5 indicating a dependence on the compound's polarity. Only X1 and X2 showed open channel block, while the kinetics of currents were affected only by X1 which further supports a dependence of the drug's effects on their polarity. In conclusion, GABA(A) receptors are inhibited and allosterically modulated by naturally occurring OETX analogues (except X5) and these effects are positively correlated with the compounds' polarity.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Wyrembek P,Negri R,Appendino G,Mozrzymas JW

doi

10.1016/j.ejphar.2012.03.005

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

35-42

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(12)00245-2

journal_volume

683

pub_type

杂志文章

在线工具

Inhibitory effects of oenanthotoxin analogues on GABAergic currents in cultured rat hippocampal neurons depend on the polyacetylenes' polarity.