Nimodipine and TMB-8 potentiate the AMPA-induced lesion in the basal ganglia.
Acute injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) into the rat globus pallidus leads to calcium precipitation, neuronal death and gliosis. In order to determine whether L-type calcium channels and/or release of Ca(2+) from intracellular stores contribute to the effects of AMPA, nimodipine and 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) were administered in combination with AMPA. Nimodipine, but not TMB-8, tended to exacerbate the calcification process initiated by AMPA; the AMPA/nimodipine/TMB-8 combination produced much more calcium deposition than AMPA (+62%, P<0.05). AMPA alone induced a slight but not significant astroglial reaction. Nimodipine slightly enhanced the astroglial reaction triggered by AMPA, whereas TMB-8 doubled it (P<0.001 versus AMPA). These data suggest that blockade of L-type calcium channels by nimodipine enhances calcium imbalance triggered by AMPA, and the calcium release from the endoplasmic reticulum does not participate in the AMPA-induced calcification.
Unitat de Bioquimica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Barcelona, Spain. vpefat@iibb.csic.es
Valérie
V
Petegnief
Gloria
G
Ursu
Fabian
F
Bernal
Nicole
N
Mahy
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology; D004357:Drug Synergism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D009553:Nimodipine; D005707:Gallic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid