Differences Between Physiological and Pharmacological Actions of Taurine

Abstract

In many experimental studies, pharmacological levels of taurine have been used to study physiological functions of taurine. However, this approach is unlikely to be fruitful, as pharmacological administration increases extracellular taurine, while physiological actions of taurine require alterations in intracellular taurine. Recognizing that different mechanisms might underlie the pharmacological and physiological actions of taurine, cardiac properties before and after exposure to various extracellular or intracellular concentrations of taurine were examined. To assess the effect of physiological taurine, myocardial contractility and metabolic status were compared in hearts containing different intracellular taurine concentrations. By contrast, the pharmacological actions of taurine were assessed in normal hearts perfused with buffer containing or lacking 10 mM taurine. Both pharmacological and physiological taurine increased contractile function and oxygen consumption. Yet, the pharmacological actions of taurine on contractile function were dependent on the L-type Ca²⁺ channel, while the sarcoplasmic reticular Ca²⁺ ATPase contributed to the physiological actions of taurine. ATP generation from available substrates, glucose, fatty acids, and acetate was increased for both the physiological and pharmacological actions of taurine. However, taurine supplementation enhanced ATP generation by elevating respiratory chain complex I activity and by stimulating metabolic flux through reductions in the NADH/NAD⁺ ratio, while the pharmacological actions of taurine can be traced to elevations in [Ca²⁺]_i and the observed positive inotropic effect. Thus, the mechanisms underlying the pharmacological actions of taurine on contractile function and energy metabolism are entirely different than those contributing to the physiological actions of taurine.

Keywords: ATP biosynthesis; Ca2+ transport; Fatty acid oxidation; Glucose oxidation; Mitochondrial function; NADH/NAD+ ratio; PPARα; Taurine deficiency.