Abstract |
The effects of agents which affect the action of nitric oxide (NO) were studied intracellularly on the ischemia-induced changes in membrane potential of single CA1 pyramidal neurons of the rat hippocampal slice preparations. The N-methyl-D-aspartate ( NMDA) receptor antagonists, (+/-)- 2-amino-5-phosphonopentanoic acid (AP5, 250 microM) or Co2 (2 mM) restored the membrane potential in more than 80% of the neurons. In about 60% of the neurons, the membrane potential was partially recovered as a result of exposure to the NO synthase inhibitor, NG-nitro-L-arginine (100 microM). The NO scavengers, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ( carboxy-PTIO, 300 microM) and hemoglobin (10 microM) restored the membrane potential in all neurons examined. Superoxide dismutase (50 U/ml) protected about 75% of the neurons from irreversible membrane dysfunction. It is concluded that the release of NO induced by experimental ischemia may result in the irreversible membrane dysfunction, and that a NO scavenger, carboxy-PTIO, prevents the ischemic changes in membrane potential. With respect to ischemic brain damage, the neuroprotection provided by carboxy-PTIO may have clinical relevance in the management of a variety of neurological conditions.
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Authors | M Onitsuka, S Mihara, S Yamamoto, M Shigemori, H Higashi |
Journal | Neuroscience research
(Neurosci Res)
Vol. 30
Issue 1
Pg. 7-12
(Jan 1998)
ISSN: 0168-0102 [Print] Ireland |
PMID | 9572575
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoates
- Hemoglobins
- Imidazoles
- Receptors, N-Methyl-D-Aspartate
- 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
- Nitroarginine
- Nitric Oxide
- Cobalt
- 2-Amino-5-phosphonovalerate
- Nitric Oxide Synthase
- Superoxide Dismutase
- Glucose
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Topics |
- 2-Amino-5-phosphonovalerate
(pharmacology)
- Animals
- Benzoates
(pharmacology)
- Cell Membrane
(drug effects, physiology)
- Cobalt
(pharmacology)
- Glucose
(pharmacology)
- Hemoglobins
(pharmacology)
- Hippocampus
(physiology)
- Hypoxia
- Imidazoles
(pharmacology)
- In Vitro Techniques
- Ischemic Attack, Transient
(physiopathology)
- Male
- Membrane Potentials
(drug effects, physiology)
- Nitric Oxide
(physiology)
- Nitric Oxide Synthase
(antagonists & inhibitors)
- Nitroarginine
(pharmacology)
- Pyramidal Cells
(drug effects, physiology)
- Rats
- Rats, Wistar
- Reaction Time
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors)
- Superoxide Dismutase
(pharmacology)
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