Inhibition of L-type Calcium Current in Rat Ventricular Cells by the Tyrosine Kinase Inhibitor, Genistein and its Inactive Analog, Daidzein

Yokoshiki, Hisashi; Sumii, Kotaro; Sperelakis, Nicholas

doi:10.1006/jmcc.1996.0075

Cited by 91 publications

(70 citation statements)

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“…These observations suggest that genistein may increase myofilament Ca 2ϩ sensitivity in addition to increasing the Ca 2ϩ transient. Our findings of a lack of effect of daidzein on cell shortening initially appear to be at odds with previous studies show- ing that daidzein inhibits I Ca,L (Yokoshiki et al, 1996;Ogura et al, 1999). However, it is possible that daidzein also increases myofilament Ca 2ϩ sensitivity in a similar way to genistein.…”

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confidence: 94%

“…All three isoflavones directly relax arterial ring preparations in vitro (Figtree et al, 2000;Chin-Dusting et al, 2001), and genistein and daidzein have been reported to inhibit the L-type Ca 2ϩ current, I Ca,L , in isolated cardiac myocytes (Yokoshiki et al, 1996;Ogura et al, 1999). It has been assumed that this results in an overall inhibition of cell contraction, although this has not been well explored.…”

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confidence: 99%

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Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

Liew

Williams²,

Collins³

et al. 2002

J Pharmacol Exp Ther

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Soy-derived isoflavones appear to possess cardioprotective properties, although the precise nature of this protection and the particular isoflavones responsible remain unclear. We hypothesized that isoflavones may differ in their cardiac actions in view of their varying affinities for the estrogen receptor and differences in ability to inhibit tyrosine kinase. We investigated the direct effects of three closely related isoflavones, genistein, daidzein, and equol (a metabolite of daidzein formed by gut microflora), on the contractile function of isolated guinea pig ventricular myocytes. Genistein (10 and 40 M) significantly increased cell shortening and the Ca 2ϩ transient (measured using indo-1). In contrast, equivalent concentrations of equol produced the opposite effect, decreasing cell shortening and the Ca 2ϩ transient, whereas daidzein was without effect. The opposing actions of genistein and equol were still observed in the presence of the specific estrogen receptor antagonist ICI 182,780 (10 M). However, the stimulatory actions of genistein were markedly reduced in the presence of the potent phosphotyrosine phosphatase inhibitor, bpV(phen). Both genistein and equol significantly inhibited the peak L-type Ca 2ϩ current. We conclude that genistein and equol affect the contractile function of ventricular myocytes in opposing ways despite a common initial action of Ca 2ϩ current antagonism. These differences occur independently of the estrogen receptor but may be partly related to the unique actions of genistein as a tyrosine kinase inhibitor. Furthermore, isoflavone metabolites, such as equol, may be more biologically active than their precursors and have a greater role in cardioprotection than previously realized.

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confidence: 94%

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confidence: 99%

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

Liew

Williams²,

Collins³

et al. 2002

J Pharmacol Exp Ther

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“…Genistein inhibited voltage-dependent Na ϩ channels, whereas daidzein had moderate effects, and genistin had a weak effect (24). Bath application of genistein decreased the L-type Ca 2ϩ current of rat ventricular cells in a concentrationdependent manner, and daidzein had nearly the same inhibitory effect on Ca 2ϩ currents (42). These results suggest that the effect of genistein may be caused by the direct blocking of Ca 2ϩ channels.…”

Section: Discussionmentioning

confidence: 79%

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Kim

Ahn

Choi

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Furthermore, genistein treatment lowered the density of the immunoreactive material in GH cells of ewes, which indicates decreased hormone storage [10]. Daidzein, although a weak tyrosinekinase inhibitor [24], fashions in a similar manner as genistein in orchidectomized andropausal rats, which opens the space for some other possible mechanisms of soy isofl avone actions pertinent to GH cells. Literature data indicate the possible alterations in somatostatin receptors (SSTRs) expression after genistein application in vitro, as a matter of fact the SSTR1 downregulation, as well as the SSTR2 and SSTR5 upregulation [25].…”

Section: Discussionmentioning

confidence: 99%

Immuno-histomorphometric and -fluorescent characteristics of GH cells after treatment with genistein or daidzein in an animal model of andropause

Ajdžanović¹,

Medigović²,

Živanović³

et al. 2014

Acta Veterinaria

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Somatopause, the complex aspect of andropause, is recognizable by reduced growth hormone - GH/insulin-like growth factor 1 axis function in the ageing male. Soy isoflavones (usually genistein and daidzein), which are known for their beneficial effects in the treatment of ageing symptoms, are active in the pituitary, as well. The immunohistomorphometric and -fluorescent characteristics of pituitary growth hormone secreting cells, in an animal model of andropause, were examined after a treatment with genistein or daidzein. Andropausal Wistar rats were divided into sham operated, orchidectomized and genistein or daidzein treated orchidectomized groups. Genistein or daidzein (30 mg/kg/day) were administered subcutaneously for three weeks, while sham operated and orchidectomized groups received the vehicle alone. Growth hormone secreting cells were identified by the peroxidase-antiperoxidase immuno-histochemical, and immuno-fluorescent procedure. The main characteristic of growth hormone secreting cells in soy isoflavones treated groups is a weaker immuno-histochemical staining and immuno-fluorescent signal compared to sham operated and orchidectomized groups. The growth hormone secreting cell volume in orchidectomized +genistein or +daidzein groups is by 13.8% and 11.9% (p<0.05) smaller respectively, in comparison with the orchidectomized group. In orchidectomized +genistein or +daidzein groups, the growth hormone secreting cells relative volume density is by 62.5% and 61.0% lower (p<0.05) respectively than for the sham operated group, and decreased by 65.4% and 64.0% (p<0.05) respectively, compared to the orchidectomized group. It can be concluded that chronic genistein or daidzein treatment, in an animal model of andropause, attenuates immunohistomorphometric and -fluorescent characteristics of growth hormone secreting cells.

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Inhibition of L-type Calcium Current in Rat Ventricular Cells by the Tyrosine Kinase Inhibitor, Genistein and its Inactive Analog, Daidzein

Cited by 91 publications

References 0 publications

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

Inhibition of Kv4.3 by genistein via a tyrosine phosphorylation-independent mechanism

Immuno-histomorphometric and -fluorescent characteristics of GH cells after treatment with genistein or daidzein in an animal model of andropause

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