insights on the mecanism of blockade of voltage-gated Na+ channels by eugenol. (2008)
- Authors:
- Autor USP: CASSOLA, ANTONIO CARLOS - ICB
- Unidade: ICB
- Assunto: FISIOLOGIA (HUMANO)
- Language: Português
- Abstract: Objetivos: We have shown that eugenol (EUG, 2-methoxy-4-(2-propenyl)phenol), a phenylpropene used in dentistry as an analgesic, blocks fast, reversibly and with low affinity voltage-gated Na+ channels (Nav). In order to get some insight on the binding site of eugenol in the channel we have investigated the effect of terpenoids while partially blocking the channels by lidocaine LID, a well known blocker. In a previous work the effects of eugenol and lidocaine were tested and compared. In dose-effect curves the IC50 of both drugs are: EUG: 2.28±0.104 and LID: 1.42±0.169 mM. LID, differently from EUG, display a pronounced frequency dependent effect. But more interesting for the purposes of the present results, are the Hill coeffcients. For LID the coefficient is 1.02, coherent with a single site binding, while for EUG the coefficient is 1.96. The straight forward interpretation is a model with 2 binding sites. Métodos e resultados: Macroscopic Na+ currents were recorded in sensory neurons from rat dorsal root ganglia, by whole-cell patch-clamp technique. We have analysed dose-response curves for LID in the continuous presence of EUG, at concentration blocking approximately 25 % of the control current, and repeated the curve for EUG in the presence of LID, at a concentration blocking one fourth of the total current. The values of control current were about 10 nA. The presence of EUG enhances LID affinity for the binding site: IC50 for the remaining channels isconsistently reduced from 1.42±0.17 to 0.73±0.13 (p<0.02), without changing the Hill coefficient (from 1.02±0.113 to 1.02±0.167). LID also affects EUG effect, but in different respect. The IC50 is not signficantly changed from (2.28±0.10 to 1.84±0.27 mM). However the Hill coefficient is signicantly reduced from 1.96±0.16 to 0.98±0.14 (p<0.001). Conclusão: On the basis of Hill coefficient analysis, one concludes that the blocking effect of EUG ís due to at least two binding sites in the Nav channel. One of the binding sites is shared by EUG and LID. Furthermore, EUG binding somewhere in the protein changes the affinity of the binding site for LID.
- Imprenta:
- Publisher: Comissão de Cultura e Extensão Universitária do ICB/USP
- Publisher place: São Paulo
- Date published: 2008
- Source:
- Título do periódico: Resumos
- Conference titles: Congresso do Instituto de Ciências Biomédicas da Universidade de São Paulo
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ABNT
SOUZA, J. L. C. e CASSOLA, Antonio Carlos. insights on the mecanism of blockade of voltage-gated Na+ channels by eugenol. 2008, Anais.. São Paulo: Comissão de Cultura e Extensão Universitária do ICB/USP, 2008. . Acesso em: 23 abr. 2024. -
APA
Souza, J. L. C., & Cassola, A. C. (2008). insights on the mecanism of blockade of voltage-gated Na+ channels by eugenol. In Resumos. São Paulo: Comissão de Cultura e Extensão Universitária do ICB/USP. -
NLM
Souza JLC, Cassola AC. insights on the mecanism of blockade of voltage-gated Na+ channels by eugenol. Resumos. 2008 ;[citado 2024 abr. 23 ] -
Vancouver
Souza JLC, Cassola AC. insights on the mecanism of blockade of voltage-gated Na+ channels by eugenol. Resumos. 2008 ;[citado 2024 abr. 23 ] - Condutâncias iônicas da membrana basolateral do epitélio da bexiga urinária de anfíbios: ii. Relação com a bomba 'NA' / k
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