Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors

G-protein coupled receptors arc transmembrane proteins widely expressed in cells and their transduction pathways are mediated by controlling second messenger levels through different G-protein interactions. Many of these receptors have been described as involved in the physiopathology of neurodegenerative diseases and even considered as potential targets for the design of novel therapeutic strategies. Endogenous and synthetic allosteric and orthosteric selective ligands are able to modulate GPCRs at both gene and protein expression levels and can also modify their physiological function. GPCRs that coexist in the same cells can homo- and heteromerize, therefore, modulating their function. Adenosine receptors are GPCRs which stimulate or inhibit adcnylyl cyclase activity through G(i)/G(s), protein and are involved in the control of neurotransmitter release as glutamate. In turn, metabotropic glutamate receptors arc also GPCRs which inhibit adenylyl cyclasc or stimulate phospholipase C activities through G(i) or G(q) proteins, respectively. In recent years, evidence of crosstalk mechanisms between different GPCRs have been described. The aim of the present review was to summarize the described mechanisms of interaction and crosstalking between adenosine and metabotropic glutamate receptors, mainly of group I, in both in vitro and in vivo systems, and their possible use for the design of novel ligands for the treatment of neurodegenerative diseases.