Guanine Nucleotides Inhibit cAMP Accumulation Induced by Metabotropic Glutamate Receptor Activation |
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Authors: | Tasca Carla I Cardoso Luciana F Martini Lúcia H Ramírez Galo Souza Diogo O |
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Institution: | (1) Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, 90035–003 Porto Alegre, RS, Brasil;(2) Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040–900 Florianópolis, SC, Brasil;(3) Centro de Biologia Molecular, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid España |
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Abstract: | Metabotropic glutamate receptors (mGluRs) have been shown to modulate adenylate cyclase activity via G-proteins. In the present study we report similar results to the previously observed in the literature, showing that glutamate and the metabotropic agonists, 1S,3R-ACPD or quisqualate induced cAMP accumulation in hippocampal slices of young rats. Moreover, guanine nucleotides GTP, GDP or GMP, inhibited the glutamate-induced cAMP accumulation. By measuring LDH activity in the buffer surrounding the slices, we showed that the integrity of the slices was maintained, indicating that the effect of guanine nucleotides was extracellular. GMP, GDP -S or Gpp(NH)p abolished quisqualate-induced cAMP accumulation. GDP -S or Gpp(NH)p but not GMP inhibited 1S,3R-ACPD-induced cAMP accumulation. The response evoked by glutamate was also abolished by the mGluR antagonists: L-AP3 abolished glutamate-induced cAMP accumulation in a dose-dependent manner and MCPG was effective only at the 2 mM dose. DNQX was ineffective. We are reporting here, an inhibition induced by guanine nucleotides, via an extracellular site (s), similar to the observed with classical glutamate antagonists on a cellular response evoked by mGluR agonists. |
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Keywords: | Glutamate 1S 3R-ACPD guanine nucleotides mGluRs (metabotropic glutamate receptors) |
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