Taurine enhancement of calcium binding to rat heart sarcolemma

European Journal of Pharmacology, 1986

Positive inotropic effect of some taurine-related compounds on guinea-pig ventricular strips perfused with low calcium medium, European J. Pharmacol. 124 (1986) 129-133.

Biochemical Pharmacology, 1981

In the ventricular sarcolemma of guinea-pig heart two uptake systems are present, a high affinity and a low affinity one. The uptake is Na-, K', Mg'+ dependent and Ca" independent, In the absence of Mg'+ only one uptake system is present. p-alanine, hypotaurine, homotaurine and guanidethylsulphonate inhibit the uptake of (3H]taurine; isethionic acid increases it.

European Journal of Pharmacology, 1980

The mechanism of the adrenergic stimulation of taurine influx in the heart, European J. Pharmacol. 61 (1980) 217--223.

Biochemical Pharmacology, 1981

Taurine uptake by guinea-pig hypertrophic heart sarcolemma vesicles was sodium-dependent and kinetic analysis suggested the presence of only one uptake system. The apparent K,,, and V,,,,, were the following; 2.5 x 10 ' M and 0.43 pmoles.mg ' protein min-' respectively. The uptake was specific and was inhibited by all analogues tested, except isethionic acid. The uptake was also inhibited by NaF.

Journal of Molecular and Cellular Cardiology, 1984

Journal of Molecular and Cellular Cardiology, 1986

The effect of taurine on ~-and/~-mediated positive inotropic effects was investigated in guinea-pig ventricular strips. Loading with taurine dose-dependently antagonized the phenylephrine-induced positive inotropic effect while it was ineffective on ]~-mediated positive inotropic effect. The superfusion with a taurine-free medium determined a loss of intracellular taurine, while the loading with 20 mM taurine prevented this depletion. Preincubation of cardiac membranes with different concentrations of taurine (1 to 20 mM) decreased 3Hprazosin binding, and the saturation curve obtained after preincubation of cardiac membranes with 20 mM taurine showed that taurine had a more marked effect on the number of" binding sites. In both experimental models, ]~-alanine did not mimic any taurine effects, suggesting that taurine acdons might be specific.

Clinical Science, 2002

Obstetric cholestasis is characterized by raised bile acids, and can be complicated by intrauterine death. We have shown that the bile acid taurocholate causes loss of synchronous beating, bradycardia and cessation of contraction in cultured rat cardiomyocytes Clin. Sci. 100, [363][364][365][366][367][368][369]. The aim of the present study was to investigate the effect of taurocholate on cardiomyocytes further. We demonstrated a reduced rate of contraction and proportion of beating cells when rat cardiomyocytes were exposed to increasing concentrations of taurocholate (0.1-3.0 mM) ; more marked at higher concentrations (P 0.001). Using scanning ion-conductance microscopy, we also demonstrated reduced amplitude of contraction and calcium transients with taurocholate. Our observations indicate that taurocholate affects calcium release from the sarcoplasmic reticulum and this parallels changes in contractile function. The relationship between the contraction amplitude and calcium transient is not linear, particularly at higher concentrations of taurocholate. We observed different effects in individual cultured neonatal cells ; a reversible reduction in rate and amplitude of contraction in some, and irreversible oscillatory (fibrillatory) cessation of beating in others. The effects were more marked with higher concentrations. The contraction amplitude was also reduced in adult cardiomyocytes. The changes were reversible following removal of taurocholate in adult, but not in neonatal, cardiomyocytes exposed to higher concentrations ( 0.3 mM) (P 0.001). In conclusion we have demonstrated that the bile acid taurocholate can cause different types of dysrhythmia in individual cardiomyocytes. These results provide further support for the hypothesis that obstetric cholestasis may produce cardiac-related sudden intrauterine death.

Advances in Experimental Medicine and Biology, 2002

Amino Acids, 1998

derivative of furoindolinone, is a novel cardiotonic agent that was designed to have both -adrenoceptor-blocking and cardiotonic activity. The aim of this study was to clarify the mode of action of UK-1745 in the canine and rabbit myocardium. UK-1745 elicited a weak but definite concentration-dependent positive inotropic effect in association with a decrease in the total duration of contraction: in particular, a decrease in the relaxation time in isolated canine right ventricular trabeculae. The maximum positive inotropic effect of UK-1745 was achieved at 3×10 −5  and amounted to approximately 15% of the maximum response to isoproterenol. The EC 50 for the positive inotropic effect of UK-1745 was 3.3×10 −6 . Carbachol, a muscarinic receptor agonist, at 3×10 −6  completely inhibited the positive inotropic effect of UK-1745. UK-1745 shifted the concentration-response curve for isoproterenol to the right with pA 2 value of 5.70. By contrast, UK-1745 at 3×10 −7 to 3×10 −5  shifted the concentration-response curve for forskolin to the left. In aequorin-loaded ventricular trabeculae, UK-1745 induced a positive inotropic effect that was accompanied by an increase in Ca 2+ transients. It did not affect the relationship between the amplitude of Ca 2+ transients and peak force as compared with that associated with elevation of the extracellular concentration of Ca 2+ ions ([Ca 2+ ] o ). The level of cyclic AMP in tissue was not significantly increased at 3×10 −5  UK-1745. The present results indicate that UK-1745 exerts a positive inotropic effect mainly via a cyclic AMP-dependent mechanism but, in addition, it has -adrenoceptor-blocking activity over the same range of concentrations. A drug with such a pharmacological profile might have the potential advantage of avoiding Ca 2+ overload and superfluous oxygen consumption, which may contribute to the unfavorable effects of novel cardiotonic agents that act purely by inhibition of phosphodiesterase III.

2005

The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca 2+ on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca 2+ -free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca 2+ -free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca 2+ chelator EGTA (1 mM) potentiated Ca 2+ depletion-evoked taurine release. The substitution of CaCl 2 by choline chloride did not alter the observed effect. Ca 2+ -free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1 mM), suggesting that in Ca 2+ depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2 0 -disulfonate (1 mM) did not attenuate the taurine release evoked by Ca 2+ depletion. The non-specific blocker of voltage-sensitive Ca 2+ channels NiCl 2 (0.65 mM) enhanced taurine release in the presence of Ca 2+ . CdCl 2 (0.25 mM) had no effect under these conditions. However, both CdCl 2 and NiCl 2 attenuated the effect of Ca 2+ -free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca 2+ and increased non-specific influx of Na + through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca 2+ depletion. #