Glutamatergic system: Another target for the action of porphyrinogenic agents

The N-methyl-diethyl-aspartate (NMDA) receptor has been reported to play an important role in several acute and chronic neuropathologic syndromes. 5-aminolevulinic acid (ALA) accumulates in acute porphyrias due to a deficiency in the heme biosynthetic pathway. Considering that glutamate uptake inhib...

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Detalles Bibliográficos
Autores principales: Lavandera, Jimena Verónica, Fossati, Mariana, Azcurra, Julio Marcos, Batlle, Alcira María del Carmen, Buzaleh, Ana María
Publicado: 2009
Materias:
Glutamatergic system
N-methyl-diethyl-aspartate
Porphyric neuropathy
Porphyrinogenic agents
allylisopropylacetamide
aminolevulinic acid
glutamic acid
isoflurane
n methyl dextro aspartic acid receptor
animal experiment
animal model
animal tissue
article
binding affinity
brain cortex
cerebellum
controlled study
drug effect
drug mechanism
male
mouse
neuropathy
nonhuman
porphyria
Aminolevulinic Acid
Animals
Barbital
Cerebellum
Cerebral Cortex
Enflurane
Ethanol
Griseofulvin
Isoflurane
Male
Mice
Porphyrinogens
Receptors, N-Methyl-D-Aspartate
Mus
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n1_p23_Lavandera
http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p23_Lavandera
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:The N-methyl-diethyl-aspartate (NMDA) receptor has been reported to play an important role in several acute and chronic neuropathologic syndromes. 5-aminolevulinic acid (ALA) accumulates in acute porphyrias due to a deficiency in the heme biosynthetic pathway. Considering that glutamate uptake inhibition caused by ALA could be one of the reasons conducing to porphyric neuropathy, it was of interest to evaluate the effect of porphyrinogenic agents on NMDA glutamatergic system. To this end receptor levels and apparent affinity (Kd) were analyzed in mice brain cortex and cerebellum. NMDA levels were diminished after chronic Isoflurane anaesthesia in brain cortex. In cerebellum, a diminution was observed after acute Enflurane and Isoflurane and allylisopropylacetamide, while ethanol administration showed a significant increase. ALA administration diminished NMDA levels only in cerebellum. Affinity constant was only reduced in brain cortex after chronic Isoflurane treatment. In conclusion, glutamatergic system appears to be involved in the action of some of the porphyrinogenic drugs studied mainly in cerebellum. Receptors regulation should therefore be considered an important mechanism in the cellular response to specific drugs, with the aim of designing new therapies and elucidating the mechanisms leading to porphyric neuropathy and acute attack triggering. Copyright © 2009 C.M.B. Edition.

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