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Human Heart Glutamate Receptors—Implications for Toxicology, Food Safety, and Drug Discovery
1 Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada K1A-OL2, P.L. 2202D2 Correspondence: Address correspondence to: Olga Pulido, Food Directorate, Bureau of Chemical Safety HPFB, Health Canada, Banting Research Center, Ottawa, Ontario, Canada P.L. 2202D2, K1A 0L2; e-mail: OlgaPulido{at}hc-sc.gc.ca Excitatory amino acids (EAAs) mediate their effects through the glutamate receptors (GluRs) in the brain. GluRs play an important role in the treatment of a variety of neuropsychiatric conditions and are central to the neurotoxicity of EAAs such as domoic and kainic acid. Unstained histological preparations of human heart tissues were used for the histopathological assessment, the anatomical identification of specific cardiac structures and the presence of the GluRs. Immunohistochemical stains with the biomarkers protein gene product (PGP 9.5) and the neurofilaments (NF 160 and NF 200) were used to identify neural structures and the components of the conducting system. Several subtypes of GluRs were differentially expressed and each had a specific distribution. In contrast to nonhuman primates, GluRs are more widely expressed in humans, where the working myocardium and the wall of blood vessels stained for GluRs. The immunolabelling was observed within the specialized structures of the conducting system, intramural nerves, and ganglia cells. These receptors may be involved in important cardiac functions such as contraction, rhythm, coronary circulation, and thus may be implicated in the pathobiology of some cardiac disease. The GluRs in the heart could be targets for the effects of excitatory compounds and is therefore an important consideration for the safety evaluation of foods and therapeutic products.
Key Words: Glutamate receptors • peripheral tissues • human heart • toxicology • immunohistochemistry Abbreviations: CNS, central nervous system • Cx, connexin • DA, domoic acid • EAAs, excitatory amino acids • GluRs, glutamate receptors • iGluRs, ionotrophic glutamate receptors • Ka, kianate • mGluRs, metabotrophic glutamate receptors • MSG, monosodium glutamate • (–)ive, negative • NF, neurofilaments • PBS, phosphate-buffered saline • (+)ive, positive • PGP 9.5, protein gene product 9.5
Toxicologic Pathology, Vol. 35, No. 3,
411-417 (2007) This article has been cited by other articles:
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