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• W2063766923 abstract "2-Amino-4,5,6,7-tetrahydrobenzo(β)thiophen-3-yl 4-chlorophenylmethanone (T62) is a member of a group of allosteric modulators of adenosine A1 receptors tested in animal models of neuropathic pain to increase the efficacy of adenosine. To determine its mechanisms at the level of receptor-G-protein activation, the present studies examined the effect of T62 on A1-stimulated [35S]guanosine-5′-O-(γ-thio)-triphosphate ([35S]GTPγS) binding in brain membranes, and by [35S]GTPγS autoradiography using the A1 agonist, phenylisopropyladenosine (PIA), to activate G-proteins. In hippocampal membranes, T62 increased both basal and PIA-stimulated [35S]GTPγS binding. The effect of T62 was non-competitive in nature, since it increased the maximal effect of PIA, with no effect on agonist potency. GTPγS saturation analysis showed that T62 increased the number of G-proteins activated by agonist but had no effect on the affinity of activated G-proteins for GTPγS. [35S]GTPγS autoradiography showed that the neuroanatomical localization of T62-stimulated [35S]GTPγS binding was identical to that of PIA-stimulated activity. The increase in PIA-stimulated activity by T62 varied between brain regions, with areas of lower A1 activation producing the largest percent modulation by T62. These results suggest a mechanism of allosteric modulators to increase the number of activated G-proteins per receptor, and provide a neuroanatomical basis for understanding potential therapeutic effects of such drugs." @default.
• W2063766923 created "2016-06-24" @default.
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• W2063766923 date "2005-04-01" @default.
• W2063766923 modified "2023-10-13" @default.
• W2063766923 title "Allosteric modulation of adenosine A ₁ receptor coupling to G‐proteins in brain" @default.
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• W2063766923 doi "https://doi.org/10.1111/j.1471-4159.2005.03044.x" @default.
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