NG-nitro-L-arginine differentially affects glutamate- or kainate-induced seizures.
The effects of nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (NNA) on seizures induced by excitatory amino acids, bicuculline, pentylenetetrazol and pilocarpine were studied in mice. NNA (10 and 40 mg kg-1, i.p.) enhanced the susceptibility to intracerebroventricular (i.c.v.) kainate (KA) which was reflected by a decrease in its convulsant dose 50% (CD50) from 0.66 nmol to 0.38 and 0.29 nmol/mouse, respectively. Also, NNA (40 mg kg-1) increased the KA-induced mortality. Conversely, NNA (40 mg kg-1) produced an anticonvulsant effect against i.c.v. glutamate whose CD50 value was significantly elevated from 0.49 mumol to 0.84 mumol/mouse. The convulsive activity of i.c.v. N-methyl-D-aspartic acid (NDMA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) was not affected by the pretreatment with NNA (40 mg kg-1). NNA (5-40 mg kg-1) also potentiated the convulsive action of systematic KA and KA-induced mortality but (up to 40 mg kg-1) remained without effect on seizures produced by bicuculline, N-methyl-D, L-aspartic acid (NMDLA), pentylenetetrazol, and pilocarpine. Only bicuculline-produced lethality was significantly enhanced. It may be concluded that the manipulation of the NO level affects differently seizures arising from a diffuse stimulation of glutamate receptors and seizures resulting from an activation of an individual subtype of these receptors. It is noteworthy that in the majority of convulsive tests used in this study, NNA exerted no modulatory effect.
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
P
P
Tutka
P
P
Klonowski
J
J
Dzieciuch
Z
Z
Kleinrok
S J
SJ
Czuczwar
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019335:Nitroarginine / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*
D019335:Nitroarginine; D018698:Glutamic Acid; D007608:Kainic Acid; D001640:Bicuculline