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Isovaline Does Not Activate GABAB ReceptorCoupled Potassium Currents in GABAB Expressing AtT-20 Cells and Cultured Rat Hippocampal Neurons
Citation
Pitman, KA and Borgland, SL and MacLeod, B and Pull, E, Isovaline Does Not Activate GABAB ReceptorCoupled Potassium Currents in GABAB Expressing AtT-20 Cells and Cultured Rat Hippocampal Neurons, PL o S One, 10, (2) Article e0118497. ISSN 1932-6203 (2015) [Refereed Article]
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Copyright Statement
Copyright 2015 Pitman et al. Licenced under Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1371/journal.pone.0118497
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-baclofeninduced
effects. Therefore, R-isovaline does not interact with recombinant or native GABAB
receptors to open K+ channels in these preparations.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | isovaline, pain, analgesia, GABA |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Basic pharmacology |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding knowledge |
| Objective Field: | Expanding knowledge in the health sciences |
| UTAS Author: | Pitman, KA (Dr Kimberley Pitman) |
| ID Code: | 102675 |
| Year Published: | 2015 |
| Web of Science® Times Cited: | 3 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2015-09-03 |
| Last Modified: | 2017-11-06 |
| Downloads: | 357 View Download Statistics |
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