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Titolo:
Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervus system of the rat
Autore:
Khan, WA; Dechkovskaia, AM; Herrick, EA; Jones, KH; Abou-Donia, MB;
Indirizzi:
Duke Univ, Ctr Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 Pharmacol & Canc Biol, Durham, NC 27710 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 57, anno: 2000,
pagine: 112 - 120
SICI:
1096-6080(200009)57:1<112:ASECDR>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCARINIC RECEPTORS; HIGH-AFFINITY; GROWTH-FACTOR; CHLORPYRIFOS OXON; ORGANO-PHOSPHATE; BRAIN; SOMAN; MODULATION; EXPRESSION; STRIATUM;
Keywords:
sarin; choline acetyltransferase; acetylcholinesterase; muscarinic acetylcholine receptor; nicotinic acetylcholine receptor; neurotoxicity; Gulf War;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Abou-Donia, MB Duke Univ, Ctr Med, Dept Pharmacol & Canc Biol, POB 3813, Durham, NC 27710USA Duke Univ POB 3813 Durham NC USA 27710 Durham, NC 27710USA
Citazione:
W.A. Khan et al., "Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervus system of the rat", TOXICOL SCI, 57(1), 2000, pp. 112-120

Abstract

Acute neurotoxic effects of sarin (O-isopropylmethylphosphonoflouridate) in male Sprague-Dawley rats were studied. The animals were treated with intramuscular (im) injections of either 1 x LD50 (100 mug/kg), and sacrificed at 0.5, 1, 3, 6, 15, or 20 h after treatment, or with im injections of either 0.01, 0.1, 0.5, or 1 x LD50 and sacrificed 15 h after treatment. Plasma butyrylcholinesterase (BChE) and brain regional acetylcholinesterase (AChE) were inhibited (45-55%) by 30 min after the LD50 dose. BChE in the plasma and AChE in cortex, brainstem, midbrain, and cerebellum remained inhibited for up to 20 h following a single LD50 treatment, No inhibition in plasma BChE activity was observed 20 h after treatment with doses lower than the LD50 dose. h;Midbrain and brainstem seem to be most responsive to sarin treatment at lower doses, as these regions exhibited inhibition (similar to 49% and 10%, respectively) in AChE activity following 0.1 x LD50 treatment, after 20 h. Choline acetyltransferase (ChAT) activity was increased in cortex, brainstem, and midbrain 6 h after LD50 treatment, and the elevated enzyme activity persisted up to 20 h after treatment. Cortex ChAT activity was significantly increased following a 0.1 x LD50 dose, whereas brainstem and midbrain did not show any effect at lower doses. Treatment with an LD50 dose caused a biphasic response in cortical nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (m2-mAChR) ligand binding, using [H-3]cytisine and [H-3]AFDX-384 as ligands for nAChR and mAChR, respectively. Decreases at 1 and 3 h and consistent increases at 6, 15, and 20 h in nAChR and m2-mAChR were observed following a single LD50 dose. The increase innAChR ligand binding densities was much more pronounced than in mAChR. These results suggest that a single exposure of sarin, ranging from 0.1 to 1 xLD50, modulates the cholinergic pathways differently and thereby causes dysregulation in excitatory neurotransmission.

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Documento generato il 14/07/20 alle ore 18:03:44