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Toxicologic Pathology
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Potential Target Sites in Peripheral Tissues for Excitatory Neurotransmission and Excitotoxicity

Santokh S. Gill

Pathology Section, Toxicology Research Division, Bureau Chemical Safety, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Reudi W. Mueller

Pathology Section, Toxicology Research Division, Bureau Chemical Safety, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Peter F. Mcguire

Pathology Section, Toxicology Research Division, Bureau Chemical Safety, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Olga M. Pulido

Pathology Section, Toxicology Research Division, Bureau Chemical Safety, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Glutamate receptors (GluRs) are ubiquitously present in the central nervous system (CNS) as the major mediators of excitatory neurotransmission and excitotoxicity. Neural injury associated with trauma, stroke, epilepsy, and many neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases and amyotrophic lateral sclerosis may be mediated by excessive activation of GluRs. Neurotoxicity associated with excitatory amino acids encountered in food, such as domoic acid and monosodium glutamate, has also 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, with 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, food safety assessment and neurobiotechnology focusing on drugs designed to interact with GluRs should consider these tissues as potential target/effector sites.

Key Words: Glutamate receptors • liver • lung • kidney • spleen • testis • preferential localization • immunochemistry • RT-PCR

References

  • Burns GA, Stephens KE, Bensen JA (1994). Expression of mRNA for the N-methyl-D-aspartate (NMDAR 1) receptor by the enteric neurons of the rat. Neurosci Lett 170: 87-90.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Castelli MP, Ingianna A., Stefanini E., Gess GL ( 1999). Distribution of GABA (B) receptors mRNAs in the rat brain and peripheral tissues. Life Sci 64: 1321-1328.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chaudhari N., Yang H., Lamp C., Delay E., Cartford C., Than T., Roper S. (1996). The taste of monosodium glutamate: Membrane receptors in taste buds. J Neurosci 16: 3817-3826.[Abstract/Free Full Text]
  • Chenu C., Serre CM, Raynal C., Burt-Pichat B., Delmas PD (1998). Glutamate receptors are expressed by bone cells and are involved in bone reabsorption. Bone 22: 295-299.[Medline] [Order article via Infotrieve]
  • Cunningham MD, Ferkany JW, Enna SJ (1994). Excitatory amino acid receptors: A gallery of new targets for pharmacological intervention. Life Sci 54: 135-148.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Demenes D., Lleixa A., Dechesne CJ (1995). Cellular and subcellular localization of AMPA-selective glutamate receptors in the mammalian peripheral vestibular system. Brain Res 671: 83-94.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dingledine R., McBain CJ, McNamara JO (1990). Excitatory amino acid receptor in epilepsy. Trends Pharmacol Sci 11: 334-338.[CrossRef][Medline] [Order article via Infotrieve]
  • Gasic GP, Hollmann M. (1992). Molecular neurobiology of glutamate receptors. Annu Rev Physiol 54: 507-536.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gill SS. Pulido OM, Mueller RW, McGuire PF (1998). Molecular and immunological characterization of the ionotropic glutamate receptors in the rat heart. Brain Res Bull 46: 429-434.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gill SS, Pulido OM, Mueller RW, McGuire PF (1999). Immunological characterization of the metabotrophic glutamate receptors in the rat heart. Brain Res Bull 48: 143-146.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gonoi T., Mizuno N., Inagaki N., Kuromi H., Seino Y., Miyazaki J., Seino S. (1994). Functional neuronal ionotropic glutamate receptors are expressed in the non-neuronal cell line MIN6. J Biol Chem 269: 16989-16992.[Abstract/Free Full Text]
  • Hardy M., Younkin D., Tang CM, Pleasure J., Shi QY, Williams M., Pleasure D. (1994). Expression of non-NMDA glutamate receptor channel genes by clonal human neurons. J Neurochem 63: 482-489.[Web of Science][Medline] [Order article via Infotrieve]
  • Hollmann M., Heinemann S. (1994). Cloned glutamate receptors. Annu Rev Neurosci 17: 31-108.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Inagaki N., Kuromi H., Gonoi T., Okamoto Y., Ishida H., Seino Y., Kaneko T., Iwanaga T., Seino S. (1995). Expression and role of ionotropic glutamate receptors in pancreatic islet cells. FASEB J 9: 686-691.[Abstract]
  • Iverson F., Truelove J., Tryphonas L., Nera EA ( 1990). The toxicology of domoic acid administered systemically to rodents and primates. Can Dis Week Rep 16(suppl 1E): 15-19.
  • Jackson EK, Branch RA, Margoius HS, Oates JA (1985). Physiological functions of the renal prostaglandin, renin and kallikrein systems. In: The Kidney-Physiology and Pathology, Seldin DW, Giebisch G (eds). Raven Press, New York, pp 613-644.
  • Krogsgaard-Larsen P., Hansen JJ (1992). Naturally occurring excitatory amino acids as neurotoxins and leads in drug design. Toxicol Lett 46/65: 409-416.
  • Lipton SA, Gendelman HE (1995). Dementia associated with the acqiured immunodeficiency syndrome. N Engl J Med 332: 934-940.[Free Full Text]
  • Lipton SA, Rosenberg PA (1994). Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330: 613-622.[Free Full Text]
  • Mick G. (1995). Non-N-methyl-D-aspartate glutamate receptors in glial cells and neurons of the pineal gland in a higher primate. Neuroendocrinology 61: 256-264.[Web of Science][Medline] [Order article via Infotrieve]
  • Morhenn VB, Waleh NS, Mansbridge JN, Unson D., Zolotorev A., Cline P., Toll L. ( 1994). Evidence for an NMDA receptor subunit in human keratinocytes and rat cardiocytes. Eur J Pharmcol 268: 409-414.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mueller R., Gill S., Pulido O., Kapal K., Smyth P. (1996). Demonstration and differential localization of glutamate receptors in the rat and monkey (Macaca fascicularis). FASEB J 9: LB146.
  • O'Connell DP, Aherne AM, Lane E., Felder RA, Carey RM (1998). Detection of dopamine receptors D1A subtype-specific mRNA in rat kidney by in situ amplification. Am J Physiol 275: F232-F241.
  • Olney JW (1994). Excitotoxins in foods. Neurotoxicology 15: 535-544.[Web of Science][Medline] [Order article via Infotrieve]
  • Ozawa S., Kamiya H., Tsuzuki K. (1998). Glutamate receptors in the mammalian central nervous sytem. Prog Neurobiol 54: 581-618.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Peng YG, Taylor TB, Finch RE, Switzer RC, Ramsdell JS (1994). Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid. NeuroReport 5: 981-985.[Web of Science][Medline] [Order article via Infotrieve]
  • Pulido O., Mueller R., Luus L. ( 1995). Immunohistochemical localization of AMPA (amino-3-hydroxy-5-methylsioxazole-4-propionic acid) glutamate receptors (GluR) in rat and monkey and retina. Microwave (MW) antigen retrieval on paraffin sections. FASEB J 9: A373.
  • Rockhold RW, Acuff CG, Clower BR (1989). Excitotoxin-induced myocardial necrosis. Eur J Pharmacol 166: 571-576.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Said SI (1999). Glutamate receptors and asthmatic airway disease. TIBS 20: 132-135.
  • Said SI, Berisha HI, Pakbaz H. (1996). Excitotoxicity in the lung: N-methyl-D-aspartate-induced, nitric oxide-dependent, pulmonary edema is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose) polymerase. Proc Natl Acad Sci USA 93: 4688-4692.[Abstract/Free Full Text]
  • Sanada H., Yao L., Jose PA, Carey RM, Felder RA (1997). Dopamine D3 receptors in rat juxtaglomerular cells. Clin Exp Hypertens 19: 93-105.[Web of Science][Medline] [Order article via Infotrieve]
  • Sninsky CA, Brooderson RJ, Broome TA, Bergeron RJ (1994). Evidence for an N-methyl-D-aspartate (NMDA) receptor in the GI tract of guinea pigs: Studies with diethylhomospermine (DEHSPM). Gastroenterology 106: A596.
  • Suzuki CA, Hierlihy SL (1993). Renal clearance of domoic acid in the rat. Food Chem Toxicol 31: 701-706.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Truelove J., Mueller R., Pulido O., Iverson F. (1996). Subchronic toxicity study of domoic acid in the rat. Food Chem Toxicol 34: 525-529.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Tryphonas L., Iverson F., Todd Ecd, Nera EA (1990). Neuropathology of experimental domoic acid poisoning in non-human primates and rats. Can Dis Week Rep 16(suppl 1E): 15-19.
  • Villalobos C., Nunez L., Garcia-Sancho J. (1996). Functional glutamate receptors in a subpopulation of anterior pituitary cell. FASEB J 10: 654-660.[Abstract]
  • Watanabe M., Mishina M., Inoue Y. (1994). Distinct gene expression of the N-methyl-D-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland. Neurosci Lett 165: 183-186.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Weaver CD, Yao TL, Powers AC, Verdoorn TA (1996). Differential expression of glutamate receptor subtypes in rat pancreatic islets. J Biol Chem 271: 12977-12984.[Abstract/Free Full Text]
  • Winter CR, Baker RC (1995). L-Glutamate-induced changes in intracellular calcium oscillation frequency through non-classical glutamate receptor binding in cultured rat myocardial cells. Life Sci 57: 1925-1934.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Yamaguchi I., Jose PA, Mouradian M., Canessa LM, Monsma FJ, Sibley DR, Takeyasu K., Felder RA (1993). Expression of dopamine D1A receptor in proximal tubule of rat kidneys. Am J Physiol 264: F280-F285.[Web of Science][Medline] [Order article via Infotrieve]
  • Zautcke JL, Schwartz JA, Mueller EJ (1986). Chinese restaurant syndrome: A review. Ann Emerg Med 15: 1210-1213.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Zhang H., Qiao Z., Zhao Y., Zhao R. ( 1996). Transcription of dopamine DA1 receptor mRNAs in rat heart. Methods Find Exp Clin Pharmcol 18: 183-187.
  • Ziyu L., Becker J., Noe CR ( 1998). Functional expression of recombinant N-methyl-D-aspartate receptors in the yeast Saccharomyces cerevisiae. Eur J Biochem 252: 391-399.[Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 28, No. 2, 277-284 (2000)
DOI: 10.1177/019262330002800207
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