Abstract
Metabotropic glutamate receptor 1 (mGluR1) is crucial for some forms of synaptic plasticity. It is known to functionally couple to both Gq and Gs proteins, resulting in activation of phospholipase C and adenylyl cyclase, respectively. We confirmed the functional couplings of mGluR1 to different G proteins by monitoring changes in [Ca2+]i (Gq pathway) and [cAMP]i (Gs pathway) in CHO cells expressing mGluR1, by simultaneous use of Ca2+ indicator indo-1 and fluorescent proteins which report activation of protein kinase A. Application of glutamate transiently increased the [Ca2+]i within 10 s after application, and gradually increased [cAMP]i, which reached maximum several minutes later. The delayed increase in [cAMP]i was not a result caused secondarily by the rapid increase in [Ca2+]i, because the truncation form of mGluR1 (mGluR1β) evoked Ca2+ transient but failed to increase [cAMP]i, as previously reported. In addition to the differential time course of the increase in [Ca2+]i and [cAMP]i, concentration dependency was different; increase in [Ca2+]i was more sensitive to glutamate than that in [cAMP]i. Interestingly, the functional couplings of mGluR1 to Gq and Gs pathways were ligand-type dependent: glutamate activates both Gq and Gs pathway, but Gd3+ activated only Gq pathway. These results suggest that the signaling pathways mediated by mGluR1 are differentially regulated by the concentration and types of ligands. [Jpn J Physiol 55 Suppl:S131 (2005)]
