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| Content Provider | PubMed Central |
|---|---|
| Author | Pitman, Kimberley A. Borgland, Stephanie L. Macleod, Bernard Ernest, Puil |
| Editor | Barnes, Steven |
| Copyright Year | 2015 |
| Abstract | Isovaline is a non-proteinogenic amino acid that has analgesic properties. R-isovaline is a proposed agonist of the γ-aminobutyric acid type B (GABAB) receptor in the thalamus and peripheral tissue. Interestingly, the responses to R-isovaline differ from those of the canonical GABAB receptor agonist R-baclofen, warranting further investigation. Using whole cell recording techniques we explored isovaline actions on GABAB receptors coupled to rectifying K+ channels in cells of recombinant and native receptor preparations. In AtT-20 cells transfected with GABAB receptor subunits, bath application of the GABAB receptor agonists, GABA (1 μM) and R-baclofen (5 μM) produced inwardly rectifying currents that reversed approximately at the calculated reversal potential for K+ R- isovaline (50 μM to 1 mM) and S-isovaline (500 μM) did not evoke a current. R-isovaline applied either extracellularly (250 μM) or intracellularly (10 μM) did not alter responses to GABA at 1 μM. Co-administration of R-isovaline (250 μM) with a low concentration (10 nM) of GABA did not result in a response. In cultured rat hippocampal neurons that natively express GABAB receptors, R-baclofen (5 μM) induced GABAB receptor-dependent inward currents. Under the same conditions R-isovaline (1 or 50 μM) did not evoke a current or significantly alter R-baclofen-induced effects. Therefore, R-isovaline does not interact with recombinant or native GABAB receptors to open K+ channels in these preparations. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0118497 |
| Starting Page | 118497 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 2 |
| Volume Number | 10 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2015-02-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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