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Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Ferraguti, F; Crepaldi, L; Nicoletti, F; (2008) Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives. PHARMACOL REV , 60 (4) 536 - 581. 10.1124/pr.108.000166.

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Abstract

Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate ( mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca2+ from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered.

Type:Article
Title:Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives
DOI:10.1124/pr.108.000166
Keywords:CEREBELLAR PURKINJE-CELLS, LONG-TERM POTENTIATION, RAT SPINAL-CORD, GROUP-I MGLURS, PROTEIN-COUPLED RECEPTOR, INOSITOL PHOSPHOLIPID-METABOLISM, UNIPOLAR BRUSH CELLS, DORSAL-HORN NEURONS, AMINO-ACID RECEPTORS, EXCITATORY SYNAPTIC-TRANSMISSION

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