Blockade of voltage-sensitive Na(+) channels by the 5-HT(1A) receptor agonist 8-OH-DPAT: possible significance for neuroprotection.
Eur J Pharmacol
; 406(3): 319-24, 2000 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-11040337
ABSTRACT
The present study was undertaken to determine whether 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agonists interact with voltage-sensitive Na(+) or N- and P/Q-type Ca(2+) channels to reduce the influx of Na(+) and/or Ca(2+). The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) inhibited both [3H]batrachotoxinin binding to neurotoxin site 2 of the Na(+) channel in rat cortical membranes (IC(50)=5.1 microM) and veratridine-stimulated Na(+) influx into rat synaptosomes (EC(50)=20. 8 microM). The 5-HT(1A) receptor agonist flesinoxan and the 5-HT(1A) receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) also displaced [3H]batrachotoxinin binding with similar affinities to 8-OH-DPAT, but were much less effective in reducing veratridine-stimulated Na(+) influx. All three serotonergic agents also increased [3H]saxitoxin binding to neurotoxin site 1 of the Na(+) channel. In contrast, none of these agents interacted with radioligand binding to N- or P/Q-type Ca(2+) channels. These data show that 8-OH-DPAT directly interacts with voltage-sensitive Na(+) channels to reduce Na(+) influx so providing an additional mechanism to explain how it functions as a neuroprotectant.
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Base de dados:
MEDLINE
Assunto principal:
8-Hidroxi-2-(di-n-propilamino)tetralina
/
Agonistas do Receptor de Serotonina
/
Fármacos Neuroprotetores
/
Bloqueadores dos Canais de Sódio
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article