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- W2041754190 abstract "Vanilloid agonists such as capsaicin activate ion flux through the TRPV1 channel, a heat- and ligand-gated cation channel that transduces painful chemical or thermal stimuli applied to peripheral nerve endings in skin or deep tissues. We have probed the SAR of a variety of 1,4-dihydropyridine (DHP) derivatives as novel ‘enhancers’ of TRPV1 activity by examining changes in capsaicin-induced elevations in 45Ca2+-uptake in either cells ectopically expressing TRPV1 or in cultured dorsal root ganglion (DRG) neurons. The enhancers increased the maximal capsaicin effect on 45Ca2+-uptake by typically 2- to 3-fold without producing an action when used alone. The DHP enhancers contained 6-aryl substitution and small alkyl groups at the 1 and 4 positions, and a 3-phenylalkylthioester was tolerated. Levels of free intracellular Ca2+, as measured by calcium imaging, were also increased in DRG neurons when exposed to the combination of capsaicin and the most efficacious enhancer 23 compared to capsaicin alone. Thus, DHPs can modulate TRPV1 channels in a positive fashion." @default.
- W2041754190 created "2016-06-24" @default.
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- W2041754190 date "2008-10-01" @default.
- W2041754190 modified "2023-10-18" @default.
- W2041754190 title "Structure–activity relationships of 1,4-dihydropyridines that act as enhancers of the vanilloid receptor 1 (TRPV1)" @default.
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- W2041754190 doi "https://doi.org/10.1016/j.bmc.2008.08.048" @default.
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