Inhibition of Ca2+uptake into A7r5 vascular smooth muscle cells by farnesollack of effect on membrane fluidity and Ca2+‐ATPase activities
作者:
Jean-Baptiste Roullet,
Kim-H Sang,
Ulrich Luft,
Mitsuake Watanabe,
Keiichi Otsuka,
David McCarron,
Marie-Aude Devynck,
期刊:
Journal of Hypertension
(OVID Available online 1997)
卷期:
Volume 15,
issue 12
页码: 1723-1728
ISSN:0263-6352
年代: 1997
出版商: OVID
关键词: farnesol;isoprenoids;smooth muscle cells;membrane fluidity;Ca2+-ATPase
数据来源: OVID
摘要:
BackgroundPrevious studies have shown that farnesol, a 15-carbon nonsterol derivative of mevalonic acid, inhibits vasoconstriction. Because of its lipophilic properties, we hypothesized that farnesol increased membrane dynamics, thus reducing uptake of Ca2+and contraction.ObjectiveTo characterize the effect of farnesol on cell membrane fluidity.DesignThe study was conducted using A7r5 cells, a rat aortic vascular smooth muscle cell line. Inhibition of Ca2+uptake by farnesol was first established in these cells. Then, the effect of farnesol on membrane dynamics was determined. Finally, to ascertain that activation of Ca2+extrusion and reuptake processes by farnesol did not occur, Ca2+-ATPase activity was examined.MethodsMembrane fluidity in cell homogenates was estimated using two fluorescent dyes (1,6-diphenyl-1,3,5-hexatriene) and (1-[-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene). Ca2+uptake was determined by monitoring the changes in cytosolic Ca2+concentration ([Ca2+]i) in fura-2-loaded cells after addition of KCl. Ca2+-ATPase activity was measured in 100 000 ×gcell fractions.ResultsFarnesol reduced KCl-induced [Ca2+]itransients significantly (P< 0.001), but did not modify membrane dynamic properties [0.214 ± 0.007 versus 0.218 ± 0.007 (n = 10) and 0.142 ± 0.002 versus 0.146 ± 0.003 (n = 5) for 1-[-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene anisotropies, respectively; NS]. Administration of up to 30 μmol/l farnesol did not affect Ca2+-ATPase activity.ConclusionFarnesol inhibits KCl-dependent rise of [Ca2+]iin A7r5 cells. This effect of farnesol is not related to a global change in plasma membrane lipid organization or to activation of Ca2+pumps. Other mechanisms such as direct inhibition of voltage-dependent Ca2+channels could therefore explain the biologic action of farnesol in the vascular tissue.
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