Taurine antagonizes the increase in intracellular calcium concentration induced by alpha-adrenergic stimulation in freshly isolated guinea-pig cardiomyocytes.

The effect of taurine on phenylephrine alpha-adrenergic action was studied in freshly-isolated guinea-pig ventricular myocytes. Intracellular calcium concentration was measured at nearly physiological extracellular CaCl2 in both cell suspension using quin-2 (mean intracellular calcium concentration 154.0 +/- 8.0 nM, n = 24), and single myocyte with fura-2 (mean intracellular calcium concentration 159.0 +/- 20.0 nM, n = 23). Phenylephrine increased intracellular calcium concentration in both preparations. In cell suspensions in the presence of 10(-6) M propranolol and at 2.2 mM extracellular calcium concentration, phenylephrine dose-dependently (3 x 10(-7)-10(-5) M) increased intracellular calcium concentration, its effect being abolished in the presence of phentolamine. Taurine 20 mM in the incubation fluid increased taurine content in the cells from 110 +/- 7 nmol/mg to 317 +/- 49 nmol/mg of total proteins. In the range 0.5-20 mM, taurine concentration-dependently reduced the phenylephrine-induced intracellular calcium increase in cell suspensions and 20 mM taurine decreased the effect of 10(-5) M phenylephrine (measured in the presence of 10(-6) M propranolol) by about 80%. Beta-Alanine (20 mM) did not modify the phenylephrine effect. Our data show that the "protective" effect of taurine in in vitro cardiac preparations and in cardiomyocyte isolation procedures is due to its effect on cardiomyocyte intracellular calcium ion concentration, and that taurine specifically antagonizes alpha-adrenoceptor activation.

[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.

We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.

Positive inotropic effect of some taurine-related compounds on guinea-pig ventricular strips perfused with low calcium medium.

Taurine exerts a positive inotropic effect at a low calcium concentration. Of the compounds chemically related to taurine only L-cysteic and 2-aminobenzenesulfonic acid mimic taurine action. Their effect is concentration-dependent and not linked to the restoration of taurine tissue concentration in guinea-pig ventricular strips. Our data demonstrate that: (1) carbon chain length between amino and sulfonic groups is a crucial factor in the development of activity. (2) Substitution of the sulfonic group with other acid functions such as the substitution of the primary amino group or the introduction of the -COOH group onto the beta-carbon brings about a lack of activity.

Functional and binding evidence of taurine inhibition of alpha-adrenoceptor effects on guinea-pig ventricle.

The effect of taurine on alpha- and beta-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 beta-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 3H-prazosin 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, beta-alanine did not mimic any taurine effects, suggesting that taurine actions might be specific.

Effects of leucine methylester on guinea-pig atria.

Superfusion of guinea-pig atria with 10 mM l-leucine methylester leads to a mechanical arrest and to an increase in protein outflow. Homogenate of atria exhibits a decrease in the sedimentability of phosphatase acid activity as compared to control. Morphological studies reveal that leucine methylester causes not only a lysosomal swelling but also a disruption of myofibrils and slight mitochondrial damage.

The protective effects of taurine on hypoxia (performed in the absence of glucose) and on reoxygenation (in the presence of glucose) in guinea-pig heart.

In isolated guinea-pig heart submitted to hypoxia in the absence of substrate and subsequent reoxygenation 1-20 mM taurine decreases LDH release and ventricular arrhythmias, and the recovery of normal electrical and mechanical activity is increased. The taurine effect is dose-dependent, and is not mimicked by beta-alanine. Moreover, taurine reduces the increase in calcium gain of reoxygenated heart.

Inotropic effect of taurine in guinea-pig ventricular strips.

At 0.9 mM CaCl2 taurine prevented the negative inotropic effect due to low calcium concentration in guinea-pig ventricular strips but not in rat strips. This taurine effect was dose-dependent. The presence (in the perfusion medium) of beta-alanine, an inhibitor of taurine transport, antagonized the effect of taurine suggesting that the action of taurine was correlated to its transport. Neither propranolol, cimetidine nor indomethacin affected the response to taurine in guinea-pig ventricular strips.

Reoxygenation dysrhythmias in the isolated guinea-pig heart: sensitivity to prazosin, atenolol and practolol.

Isolated guinea-pig hearts were perfused aerobically for 60 min, then made anoxic for 30 min and finally reoxygenated for 30 min. The effects of prazosin, atenolol and practolol on contractility, coronary pressure, ECG and LDH release were examined. Prazosin and atenolol were able to reduce significantly the incidence of ventricular fibrillation and LDH release. The same two drugs increased the recovery of normal electrical activity after 30 min of reoxygenation. Practolol, on the other hand, was ineffective in reducing the incidence of ventricular arrhythmias and LDH release.

Effect of taurine on calcium levels and contractility in guinea-pig ventricular strips.

Taurine increases the calcium levels in guinea-pig ventricular strips at external calcium concentrations of 0.45, 0.9 and 1.8 mM. At 2.7 mM calcium, however, a decrease is observed. Analogous changes occur in contractile force. It is also seen that the superfusion of ventricular strips with taurine-free medium produces a decrease in taurine content at the end of 120 min superfusion. Taurine levels can be restored by superfusion with 10 mM taurine; a linear relationship exists between external taurine and internal taurine levels.

The effect of taurine on high potassium-and noradrenaline-induced contraction in rabbit ear artery.

1 Intraluminal administration of taurine (40 mM) did not affect the contractile tone of rabbit isolated ear artery 2 Taurine (10-80 mM) exerted a powerful concentration-dependent, vasodilator action in arteries contracted with high potassium medium. 3 In the same experimental conditions, the taurine analogues beta-alanine and homotaurine, had no effect. 4 Taurine (40-80 mM) did not affect in a significant manner the tonic component of the noradrenaline (5x10(-6 M)-induced contraction. 5 When noradrenaline (5x10(-6M) was followed by the administration of high potassium medium a further increase in intraluminal pressure was observed. Under these conditions taurine (40 mM) reversed specifically the component due to the high potassium medium.