Trans- and cis-resveratrol increase cytoplasmic calcium levels in A7r5 vascular smooth muscle cells.
The effects of trans- and cis-resveratrol on cytosolic Ca2+ concentration ([Ca2+]i) were studied using fura-2 in vascular smooth muscle cells (A7r5). Both isomers of resveratrol caused a sustained elevation in [Ca2+]i, cis-resveratrol being significantly more effective than the trans-isomer. The resveratrol-induced increase in [Ca2+]i was significantly potentiated by the previous application of low concentrations of thapsigargin, partially inhibited by nifedipine or Ni2+, and not affected by SKF 96365. In the absence of extracellular Ca2+, both isomers of resveratrol induced a transient, slow increase in [Ca2+]i, which was inhibited by the previous depletion of intracellular stores with thapsigargin and completely blocked by preincubation with TMB-8, an inhibitor of intracellular calcium release. Reintroduction of Ca2+ in the external solution after the resveratrol-induced release of Ca2+ activated the Ca2+ influx through store-operated calcium channels. The resveratrol-induced increase in [Ca2+]i in the absence of extracelullar Ca2+ partially reduced the increase in [Ca2+]i evoked by the subsequent application of thapsigargin. Our results suggest that trans- and cis-resveratrol induce a depletion of Ca2+ from the same intracellular stores released by thapsigargin and subsequent capacitative influx of Ca2+. Additionally, a direct activation of transmembrane Ca2+ influx through another type of channel may be also implicated.
Campos-Toimil
Manuel
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela A Coruña, Spain.
Elíes
Jacobo
J
Orallo
Francisco
F
D000818:Animals; D001011:Aorta; D002118:Calcium / Q000032:analysis*; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry*; D004357:Drug Synergism; D004622:Embryo, Mammalian; D007093:Imidazoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000648:ultrastructure*; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology
D007093:Imidazoles; D013267:Stilbenes; D019284:Thapsigargin; D009532:Nickel; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D000077185:Resveratrol; D002118:Calcium