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Isovaline Does Not Activate GABAB ReceptorCoupled Potassium Currents in GABAB Expressing AtT-20 Cells and Cultured Rat Hippocampal Neurons


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 2015 Pitman et al. Licenced under Creative Commons Attribution 4.0 International

DOI: doi:10.1371/journal.pone.0118497


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
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