title: Polyamine metabolism and glutamate receptor agonists-mediated excitotoxicity in the rat brain.
abstract: Putrescine (PUT) increases have been seen in a range of models of neuropathological disturbances. The present study was designed to compare the ability of various types of glutamate receptor agonist to promote excitotoxic brain damage and to examine whether a PUT increase is a general marker of excitotoxic brain damage. To that end, we evaluated features of brain damage associated with the excitotoxicity induced by both ionotropic glutamate receptor (iGluR) and metabotropic glutamate receptor (mGluR) agonists in the conscious rat and the changes produced in the regulation of polyamine metabolism. Intracerebroventricular infusion of N-methyl-D-aspartate (NMDA; 80 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 15 nmol), kainic acid (KA; 2.3 nmol), (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG; 1.5 micromol), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 2 micromol) produced similar seizure incidences (76-84%) in the rat. The convulsant episodes appeared sooner after iGluR (13-22 min) than after mGluR agonists (50-179 min). Histological analysis of the hippocampus 24 hr after seizures indicated several degrees of excitotoxic injury after equiconvulsive doses of the iGluR and mGluR agonists assayed. The agonists can be placed in the following order, according to the degree of damage they produce: AMPA > 3,5-DHPG approximately KA > NMDA > 1S,3R-ACPD. In the frontal cortex, moderate to low levels of damage were observed after all GluR agonists. Both iGluR- and mGluR-induced seizures produced an overshoot in the hippocampal and cortical PUT concentration, whereas spermidine and spermine levels were similar to control. Moreover, a concurrence of increased PUT levels and brain damage was observed, indicating that PUT is a general marker of excitotoxic brain damage.
authors.affiliation: Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Rosselló 161, 6th floor, 08036-Barcelona, Spain. lcsfat@iibb.csic.es
authors.forename: L
authors.initials: L
authors.lastname: Camón
authors.forename: N
authors.initials: N
authors.lastname: de Vera
authors.forename: E
authors.initials: E
authors.lastname: Martínez
mesh_terms: D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
chemical_list: D015317:Biogenic Polyamines; D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D017470:Receptors, Glutamate; D013096:Spermine; D018698:Glutamic Acid; D013095:Spermidine; D011700:Putrescine