Neurochemical effects of L-pyroglutamic acid.
The effect of L-pyroglutamic acid, a metabolite that accumulates in pyroglutamic aciduria, on different neurochemical parameters was investigated in adult male Wistar rats. Glutamate binding, adenylate cyclase activity and G protein coupling to adenylate cyclase were assayed in the presence of the acid. L-pyroglutamic acid decreased Na(+)-dependent and Na(+)-independent glutamate binding. Basal and GMP-PNP stimulated adenylate cyclase activity were not affected by the acid. Furthermore, rats received unilateral intrastriatal injections of 10-300 nmol of buffered L-pyroglutamic acid. Vehicle (0.25 M Tris-Cl, pH 7.35-7.4) was injected into the contralateral striatum. Neurotoxic damage was assessed seven days after the injection by histological examination and by weighing both cerebral hemispheres. No difference in histology or weight could be identified between hemispheres. These results suggest that, although capable of interfering with glutamate binding, pyroglutamate did not cause a major lesion in the present model of neurotoxicity.
de Mello
C F
CF
Departamento de Química, Universidade Federal de Santa Maria, Brasil.
De La Vega
D D
DD
Pizutti
L T
LT
Lopes
F P
FP
Rubin
M A
MA
Homerich
J G
JG
Melo
C R
CR
Somer
J E
JE
Souza
D O
DO
Wajner
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology
D006165:Guanylyl Imidodiphosphate; D018698:Glutamic Acid; D012964:Sodium; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D011761:Pyrrolidonecarboxylic Acid