The distinct role of mGlu1 receptors in post-ischemic neuronal death.
Metabotropic glutamate receptors of the mGlu(1) and mGlu(5) subtypes exhibit a high degree of sequence homology and are both coupled to phospholipase C and intracellular Ca(2+) mobilization. However, functional differences have been detected for these receptor subtypes when they are coexpressed in the same neuronal populations. Experimental evidence indicates that mGlu(1) and mGlu(5) receptors play a differential role in models of cerebral ischemia and that only mGlu(1) receptors are implicated in the pathways leading to post-ischemic neuronal injury. The localization of mGlu(1) receptors in GABA-containing interneurons rather than in hippocampal CA1 pyramidal cells that are vulnerable to ischemia has prompted studies that have provided a new viewpoint on the neuroprotective mechanism of mGlu(1) receptor antagonists. The hypothesis predicts that these pharmacological agents attenuate post-ischemic injury by enhancing GABA-mediated neurotransmission.
Pellegrini-Giampietro
Domenico E
DE
Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale G. Pieraccini 6, 50139 Florence, Italy. domenico.pellegrini@unifi.it
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002490:Central Nervous System / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*
D018696:Neuroprotective Agents; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1