| Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers. | |
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MedLine Citation:
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PMID: 10913580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors. We now report that the effects of urocanic acid on binding of a convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in brain membrane homogenates are dependent on pH of the incubation medium, the agonistic actions being enhanced at the normal pH of the skin (5.5). Using Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A) receptors, the low pH potentiated the direct agonistic action of trans-urocanic acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences between urocanic acid isomers in functional activity at one putative receptor site of immunosuppression, the GABA(A) receptor, the presence of which in the skin remains to be demonstrated. |
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Authors:
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M Uusi-Oukari; S L Soini; J Heikkilä; A Koivisto; K Neuvonen; P Pasanen; S T Sinkkonen; J K Laihia; C T Jansén; E R Korpi |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: European journal of pharmacology Volume: 400 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2000 Jul |
Date Detail:
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Created Date: 2000-10-12 Completed Date: 2000-10-12 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 11-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Clinical Pharmacology, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bicyclo Compounds, Heterocyclic / metabolism Dose-Response Relationship, Drug GABA Modulators / pharmacology* Hydrogen-Ion Concentration Immune Tolerance / radiation effects Male Rats Rats, Wistar Receptors, GABA-A / drug effects*, physiology Stereoisomerism Ultraviolet Rays Urocanic Acid / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Bicyclo Compounds, Heterocyclic; 0/GABA Modulators; 0/Receptors, GABA-A; 104-98-3/Urocanic Acid; 70636-86-1/tert-butylbicyclophosphorothionate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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