Metabotropic glutamate 1 receptor: Current concepts and perspectives

Francesco Ferraguti, Luca Crepaldi, Ferdinando Nicoletti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)536-581
Number of pages46
JournalPharmacological Reviews
Volume60
Issue number4
DOIs
Publication statusPublished - Dec 2008

Fingerprint

Metabotropic Glutamate Receptors
Pharmacology
Heterotrimeric GTP-Binding Proteins
Glutamate Receptors
Type C Phospholipases
Nervous System Diseases
Psychiatry
Glutamic Acid
Genes
metabotropic glutamate receptor type 1

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Metabotropic glutamate 1 receptor : Current concepts and perspectives. / Ferraguti, Francesco; Crepaldi, Luca; Nicoletti, Ferdinando.

In: Pharmacological Reviews, Vol. 60, No. 4, 12.2008, p. 536-581.

Research output: Contribution to journalArticle

Ferraguti, Francesco ; Crepaldi, Luca ; Nicoletti, Ferdinando. / Metabotropic glutamate 1 receptor : Current concepts and perspectives. In: Pharmacological Reviews. 2008 ; Vol. 60, No. 4. pp. 536-581.
@article{731ffa2fc4a14905a0e792b7aa0ca61c,
title = "Metabotropic glutamate 1 receptor: Current concepts and perspectives",
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.",
author = "Francesco Ferraguti and Luca Crepaldi and Ferdinando Nicoletti",
year = "2008",
month = "12",
doi = "10.1124/pr.108.000166",
language = "English",
volume = "60",
pages = "536--581",
journal = "Pharmacological Reviews",
issn = "0031-6997",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "4",

}

TY - JOUR

T1 - Metabotropic glutamate 1 receptor

T2 - Current concepts and perspectives

AU - Ferraguti, Francesco

AU - Crepaldi, Luca

AU - Nicoletti, Ferdinando

PY - 2008/12

Y1 - 2008/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58149101182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149101182&partnerID=8YFLogxK

U2 - 10.1124/pr.108.000166

DO - 10.1124/pr.108.000166

M3 - Article

C2 - 19112153

AN - SCOPUS:58149101182

VL - 60

SP - 536

EP - 581

JO - Pharmacological Reviews

JF - Pharmacological Reviews

SN - 0031-6997

IS - 4

ER -