Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity

Glutamate receptors (GluRs) are ubiquitously present in the central nervous system (CNS) as the major mediators of excitatory neurotransmission and ex citotoxicity. Neural injury associated with trauma, stroke, epilepsy, and m any neurodegenerative diseases such as Alzheimer's, Huntington's, and Parki nson's diseases and amyotrophic lateral sclerosis may be mediated by excess ive activation of GluRs. Neurotoxicity associated with excitatory amino aci ds encountered in food, such as domoic acid and monosodium glutamate, has a lso been Linked to GluRs. Less is known about GluRs outside the CNS. Recent observations suggest that several subtypes of GluRs are widely distributed in peripheral tissues. Using immunochemical and molecular techniques, the presence of GluR subtypes was demonstrated in the rat and monkey heart, wit h preferential distribution within the conducting system, nerve terminals, and cardiac ganglia. GluR subtypes NMDAR 1,GluR 2/3, and mGluR 2/3 are also present in kidney, liver, lung, spleen, and testis. Further investigations are needed to assess the role of these receptors in peripheral tissues and their importance in the toxicity of excitatory compounds. Therefore, rued safety assessment and neurobiotechnology focusing on drugs designed to inte ract with GluRs should consider these tissues as potential target/effector sites.