Flavia Franconi

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 β‐alanine and homotaurine, had no effect. 4 Taurine (40–80 mm) did not affect in a significant manner the tonic component of the noradrenaline (5 × 10−6 m)‐induced contraction. 5 When noradrenaline (5 × 10−6 m) 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.

INTERACTION OF HISTAMINE H1- AND H2-RECEPTOR ANTAGONISTS WITH HISTAMINE UPTAKE AND METABOLISM BY GUINEA-PIG ISOLATED ATRIUM AND MOUSE NEOPLASTIC MAST CELLS in vitro

1 Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea‐pig atrium and in mouse neoplastic mast cells. 2 Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide > chlorpheniramine > triprolidine > metiamide in the atrium; and burimamide > metiamide > triprolidine > chlorpheniramine, in the mast cells. 3 Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.

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.

Taurine and Diabetes

Recent studies indicate that taurine levels are reduced both in plasma3 and platelets obtained from patients with insulin-dependent diabetes mellitus (IDDM) in the absence of any complications of disease3. We have demonstrated that between plasma taurine levels and glycosylated hemoglobin levels (HbAlc) there is an inverse linear correlation indicating that taurine levels could be of some relevance in the control of metabolic state3. Moreover, when taurine levels are increased by taurine supplementation, the sensitivity of platelets obtained from IDDM patients to arachidonic acid is decreased3.

[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.

Uptake of [3H]taurine into myocardial membranes

Abstract 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 2+ dependent and Ca 2+ independent. In the absence of Mg 2+ only one uptake system is present. β-alanine, hypotaurine, homotaurine and guani-dethylsulphonate inhibit the uptake of [ 3 H]taurine; isethionic acid increases it.

Taurine-calcium interaction measured by means of 13C nuclear magnetic resonance.

Abstract Despite the fact that many of the physiological roles of taurine are still obscure, a series of experimental data have been published suggesting that taurine can have a function in the modulation of calcium fluxes at cardiac level [1–3] and at the level of liver mitochondria [4]. It was suggested that the interference of taurine with calcium fluxes could be interpreted as the result of the formation of a calcium-taurine complex [1–4]. This hypothesis was rejected in a paper of Igisu et al . [5]. We have further investigated this point by means of Fourier Transform 13 C nuclear magnetic resonance ( 13 C-FT-NMR). In recent years it was in fact demonstrated that this is a powerful tool for the study of weak ligand-metal interactions. [6].

Interaction between organic calcium‐channel blockers and taurine in vitro and in vivo

Taurine is a positive inotropic agent in guinea-pig auricles perfused with a normal calcium medium, it potentiates the positive inotropic effect of strophanthin-K (Guidotti et al 1971) and ouabain (Iwata & Fujimoto 1976). Taurine inhibits the decrease in contractile force due to a calciumfree medium (Dolara et al 1973) in the isolated and perfused heart. Furthermore the positive inotropic effect of taurine is more evident in vitro when the calcium concentration in the external medium is low (Dietrich & Diacono 1971; Bandinelli et a1 1981). There is evidence that the potentiating effect of taurine on the positive inotropic effect of ouabain is to some extent related to an accumulation of intracellular calcium in taurine-loaded heart (Iwata & Fujimoto 1976); Dolara et al(l973) also found that taurine increased calcium levels in cardiac tissue. On the other hand, taurine antagonized the negative inotropic effect of verapamil in rat isolated and perfused hearts (Chovan et al 1980). We decided to examine the interaction between methoxy verapamil (D600) and taurine in guinea-pig ventricular strips, since rat and guinea-pig hearts are known to behave differently in many respects, e.g. the digitalis response and the staircase phenomenon (Allen & Schwartz 1969). The interaction between taurine and verapamil was also studied in vivo.

Functional and binding evidence of taurine inhibition of α-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.