کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5829588 1558998 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibitory effects of oenanthotoxin analogues on GABAergic currents in cultured rat hippocampal neurons depend on the polyacetylenes' polarity
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Inhibitory effects of oenanthotoxin analogues on GABAergic currents in cultured rat hippocampal neurons depend on the polyacetylenes' polarity
چکیده انگلیسی
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 GABAA receptors (Wyrembek et al., 2010). O. crocata also contains several minor OETX analogues and in the present study we tested whether their effect on GABAA 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, GABAA receptors are inhibited and allosterically modulated by naturally occurring OETX analogues (except X5) and these effects are positively correlated with the compounds' polarity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 683, Issues 1–3, 15 May 2012, Pages 35-42
نویسندگان
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