Abstract
Group I metabotropic glutamate (mGlu) receptors consists of mGlu1 and mGlu5 receptor subtypes. These receptors are widely distributed in the central nervous system (CNS), where they preferentially mediate facilitatory signaling in neurones and glial cells, mainly by favoring phospholipase (PLC) translocation. Based on the literature so far available, group I Metabotropic glutamate receptors (mGluRs) are preferentially expressed at the postsynaptic side of chemical synapsis, where they participate in the progression of the chemical stimulus. Studies, however, have shown the presence of these receptors also at the presynaptic level, where they exert several functions, including the modulation of transmitter exocytosis. Presynaptic Group I mGluRs can be both autoreceptors regulating release of glutamate and heteroreceptors regulating the release of various transmitters, including GABA, dopamine, noradrenaline, and acetylcholine. While the existence of presynaptic release-regulating mGlu5 receptors is largely recognized, the possibility that mGlu1 receptors also are present at this level has been a matter of discussion for a long time. A large body of evidence published in the last decade, however, supports this notion. This review aims at revisiting the data from in vitro studies concerning the existence and the role of release-regulating mGlu1 receptors presynaptically located in nerve terminals isolated from selected regions of the CNS. The functional interaction linking mGlu5 and mGlu1 receptor subtypes at nerve terminals and their relative contributions as modulators of central transmission will also be discussed. We apologize in advance for omission in our coverage of the existing literature.
Highlights
Reviewed by: Luca Ferraro, University of Ferrara, Italy Bruno Pierre Guiard, University of Paris XI, France
These receptors are widely distributed in the central nervous system (CNS), where they preferentially mediate facilitatory signaling in neurones and glial cells, mainly by favoring phospholipase (PLC) translocation
This review aims at revisiting the data from in vitro studies concerning the existence and the role of release-regulating mGlu1 receptors presynaptically located in nerve terminals isolated from selected regions of the CNS
Summary
Transmitter release is a key event of central transmission. At chemical synapsis, it assures the transmission from the presynaptic to the postsynaptic component of the active synapse, allowing the propagation of the stimulus. Synaptosomes are isolated from tissue homogenates by centrifugation and purified on a Percoll gradient to eliminate contaminating particles originating from other cells, including astrocytes This is relevant in studies dedicated to the pharmacological characterization of presynaptic mGlu autoreceptors modulating glutamate release from nerve endings. The most interesting observation was that (RS)-2-Chloro5-hydroxyphenylglycine (CHPG, Table 1), a preferential mGlu receptor agonist, failed to potentiate the 4-AP-evoked [3H]glutamate release from cerebrocortical synaptosomes, while the selective mGluR1 antagonist (RS)-1-Aminoindan-1,5dicarboxylic acid (AIDA, Table 1) abolished the potentiation elicited by the mGlu1/5 broad spectrum agonist, the compound (S)-3,5-Dihydroxyphenylglycine (3,5-DHPG, Table 1) These results led to propose that presynaptic mGlu receptors did not account for the functional responses observed, but that the group I mGlu receptors under study belonged to the mGlu receptors subtype. The analysis of the concentration-effect relationship of the agonist on the [3H]D-ASP exocytosis unveiled a biphasic pattern, where peaks of potentiation were reached
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