Abstract:
:Stimulation of G-proteins coupled with metabotropic glutamate receptors (mGlu receptors) was investigated by means of guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding assay in rat hippocampal and striatal membranes. The endogenous ligand l-glutamate increased specific [(35)S]GTPγS binding in a concentration-dependent manner with a mean EC50 values of around 10μM in both brain regions, The maximal % increase over the respective basal binding was highest in cerebral cortex, intermediate in hippocampus, and lowest in striatum. The pharmacological profiles of the responses investigated with a series of glutamatergic agonists and antagonists clearly indicated that they were mediated through group II mGlu receptors, particularly mGlu2 subtype, in both brain regions. The pEC50 and relative %Emax values for a series of agonists were essentially identical in both brain regions that were also correlated with those previously reported in cerebral cortical membranes. The selective allosteric potentiator of mGlu2 receptor subtype, LY487379, potentiated the increasing effects of l-glutamate at a maximally effective concentration of 1mM on specific [(35)S]GTPγS binding, without altering the basal unstimulated binding. It is concluded that [(35)S]GTPγS binding assay is applicable to rat hippocampal and striatal membranes to detect functional activation of Gαi/o proteins coupled with mGlu2 receptors.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Odagaki Y,Kinoshita M,Toyoshima Rdoi
10.1016/j.neulet.2013.01.033subject
Has Abstractpub_date
2013-02-28 00:00:00pages
22-6eissn
0304-3940issn
1872-7972pii
S0304-3940(13)00075-Xjournal_volume
539pub_type
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