Trezza, Alfonso published the artcileFunctional, electrophysiology, and molecular dynamics analysis of quercetin-induced contraction of rat vascular musculature, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is European Journal of Pharmacology (2022), 174778, database is CAplus and MEDLINE.
Quercetin, a flavonoid abundantly present in the Mediterranean diet, is considered a vasodilator despite its recognized capability to stimulate vascular CaV1.2 channel current (ICa1.2). The present study was undertaken to assess its possible vasocontractile activity. Functional and electrophysiol. experiments were performed in vitro on rat aorta rings and tail artery myocytes along with an in-depth mol. modeling anal. The CaV1.2 channel stimulator (S)-(-)-methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (Bay K 8644) was used as reference compound Quercetin and Bay K 8644 caused a significant leftward shift of KCl concentration-response curve. Neither agent affected basal muscle tone, though in rings pre-treated with thapsigargin or 15 mM KCl they caused a strong, concentration-dependent contraction. Both quercetin and Bay K 8644 potentiated the response to Ca2+ in weakly depolarised rings. At high KCl concentrations, however, quercetin caused vasorelaxation. While Bay K 8644 stimulated ICa1.2, this effect being sustained with time, quercetin-induced stimulation was transient, although the mol. in solution underwent only marginal oxidation Quercetin transient stimulation was not affected by pre-treatment with isoprenaline, sodium nitroprusside, or dephostatin; however, it converted to a sustained one in myocytes pre-incubated with Go6976. Classical mol. dynamics simulations revealed that quercetin and Bay K 8644 formed hydrogen bonds with target sensing residues of CaV1.2 channel favoring the inactivated conformation. In conclusion, quercetin-induced stimulation of ICa1.2 promoted vasocontraction when Ca2+ buffering function of sarcoplasmic reticulum was impaired and/or smooth muscle cell membrane was moderately depolarised, as it may occur under certain pathol. conditions.
European Journal of Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H28N2O7, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem