Expression of heteromeric glycine receptor-channels in rat spinal cultures and inhibition by neuroactive steroids.

Full Abstract

Ionotropic glycine receptors were studied in cultured spinal cord neurons prepared from 17-day-old rat embryos, using whole-cell patch clamp electrophysiology. Glycine receptors of 3-17 days in vitro were characterized via subtype-specific channel blockade by micromolar picrotoxin and cyanotriphenylborate, as well as nanomolar strychnine. Potentiation by nanomolar tropisetron indicated coexpression of beta with alpha subunits. The neuroactive steroids pregnenolone sulfate and dehydroepiandrosterone sulfate, as well as alphaxalone and its 3beta epimer betaxalone inhibited the chloride current with IC(50) values of 19, 46, 16 and 208 microM, respectively, with no potentiation. Reverse transcription polymerase chain reaction and immunocytochemistry demonstrated mRNAs and proteins of alpha1, alpha2, alpha3 and beta subunits in rat spinal cord cultures. In conclusion, neuroactive steroids, both positive and negative modulators of gamma-aminobutyric-acid(A) receptors, inhibited heteromeric glycine receptors at micromolar concentrations.

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Author information

Author/s: Fodor, László (L); Boros, András (A); Dezso, Péter (P); Maksay, Gábor (G);

Affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Ltd., POB 27, H-1475 Budapest, Hungary. l.fodor(-atsign-)richter.hu

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neurochemistry international (Neurochem Int), published in England. (Language: eng)

Reference: 2006-Nov; vol 49 (issue 6) : pp 577-83

Dates: Created 2006/10/18; Completed 2006/12/12; Revised 2007/01/17;

PMID: 16784797, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Chloride Channels - drug effects
Data Interpretation, Statistical
Dehydroepiandrosterone - pharmacology
Electrophysiology
Glycine - pharmacology
Immunohistochemistry
Indoles - pharmacology
Patch-Clamp Techniques

Pregnanediones - pharmacology
RNA, Messenger - biosynthesis; genetics
Rats
Receptors, Glycine - agonists; antagonists & inhibitors; biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Fluorescence
Spinal Cord - cytology; drug effects; metabolism
Steroids - pharmacology
Taurine - pharmacology

Associated Chemicals: Chloride Channels (0) ; Indoles (0) ; Pregnanediones (0) ; RNA, Messenger (0) ; Receptors, Glycine (0) ; Steroids (0) ; Taurine (107-35-7) ; alphaxalone (23930-19-0) ; Dehydroepiandrosterone (53-43-0) ; Glycine (56-40-6) ; tropisetron (89565-68-4)

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