Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels

• Published in: Journal of physiology and biochemistry Vol. 65; no. 2; pp. 113 - 124
• Main Authors: Speroni, F., Rebolledo, A., Salemme, S., Roldán-Palomo, R., Rimorini, L., Añón, M. C., Spinillo, A., Tanzi, F., Milesi, V.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2009
• Subjects: Animal Physiology; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Calcium Channels - drug effects; Female; Genistein - pharmacology; Human Physiology; Humans; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Patch-Clamp Techniques; Pregnancy; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - secretion; Umbilical Arteries - metabolism; Músculo liso vascular humano; Calcium channels; Genistein; Canales de calcio; Human vascular smooth muscle; Genisteína; Umbilical artery; Arteria umbilical
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/BF03179062

Isoflavones are a group of natural phytoestrogens including the compound genistein. Health beneficial effects have been attributed to the consumption of this compound, but the fact that it has estrogen-like activity has raised doubts regarding its potential risk in infants, newborns, or in the fetus and placenta during pregnancy. This work is aimed at studying genistein effects on Ca 2+ handling by smooth muscle cells of the human umbilical artery (HUA). Using fluorometric techniques, we found that in these cells genistein reduces the intracellular Ca 2+ peak produced by serotonin. The same result could be demonstrated in absence of extracellular Ca 2+ , suggesting that the isoflavone reduces Ca 2+ release from the sarcoplasmic reticulum. Force measurement experiments strengthen these results, since genistein reduced the peak force attained by intact HUA rings stimulated by serotonin in a Ca 2+ -free solution. Moreover, genistein induced the relaxation of HUA rings precontracted either with serotonin or a depolarizing high-extracellular K + solution, hinting at a reduction of extracellular Ca 2+ entry to the cell. This was confirmed by whole-cell patch-clamp experiments where it was shown that the isoflavone inhibits ionic currents through voltage-operated Ca 2+ channels. In summary, we show that genistein inhibits two mechanisms that could increase intracellular Ca 2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance of fetal vessels. Taking into account that genistein is able to cross the placental barrier, these data show that isoflavones may have important implications in the regulation of feto-maternal blood flow in pregnant women who consume soy-derived products as part of their meals.