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Selective antagonism of rat inhibitory glycine receptor subunits.
- Source :
-
The Journal of physiology [J Physiol] 2004 Feb 01; Vol. 554 (Pt 3), pp. 649-58. Date of Electronic Publication: 2003 Nov 28. - Publication Year :
- 2004
-
Abstract
- Retinal ganglion cells exhibit fast and slow inhibitory synaptic glycine currents that can be selectively inhibited by strychnine and 5,7-dichlorokynurenic acid (DCKA), respectively. In this study we examined whether strychnine and DCKA selectivity correlated with the subunit composition of the glycine receptor. Homomeric alpha1, alpha2 or alpha2* glycine subunits were in vitro expressed in human embryonic kidney cells (HEK 293). In cells expressing the alpha1 subunit, responses to 200 microm glycine were blocked by 1 microm strychnine but not by 500 microm DCKA. In cells expressing the alpha2 subunit, both 1 microm strychnine and 500 microm DCKA were effective antagonists of 200 microm glycine. In cells expressing alpha2* subunits, which are much less glycine-sensitive, 10 mm glycine was inhibited by 500 microm DCKA but not by 1 microm strychnine. A single amino acid mutation in the alpha1 subunit (R196G), converted this subunit from DCKA-insensitive to DCKA-sensitive. In conclusion, the comparative effectiveness of strychnine and DCKA can be used to distinguish between the alpha1, alpha2 and alpha2* receptor responses. Furthermore, a single amino acid near the glycine receptor's putative agonist binding site may account for differences in DCKA sensitivity amongst the alpha subunits.
- Subjects :
- Animals
Arginine
Cell Line
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists administration & dosage
Glycine administration & dosage
Glycine antagonists & inhibitors
Glycine pharmacology
Glycine Agents administration & dosage
Humans
Kynurenic Acid administration & dosage
Mutation
Osmolar Concentration
Rats
Receptors, Glycine genetics
Strychnine administration & dosage
Excitatory Amino Acid Antagonists pharmacology
Glycine Agents pharmacology
Kynurenic Acid analogs & derivatives
Kynurenic Acid pharmacology
Receptors, Glycine antagonists & inhibitors
Strychnine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3751
- Volume :
- 554
- Issue :
- Pt 3
- Database :
- MEDLINE
- Journal :
- The Journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 14645455
- Full Text :
- https://doi.org/10.1113/jphysiol.2003.056309