Taurine (2-aminoethane sulfonic acid) is one of the most abundant free amino acids found in mammalian brain, heart and muscle. Taurine levels have also been shown to be altered in certain disease states. A physiological role for taurine in the maintainance of excitatory activity in muscle and nervous tissues has been suggested; however its possible mechanism of action is still uncertain.
Early work on the pharmacological actions of taurine involved its possible conversion to isethionic acid (2-hydroxyethane sulfonic acid), a strong anion. This conversion was said to lead to the conductance of cations into the cardiac cell. An analytical technique to measure isethionic acid in mammalian tissues was developed. The method involved extraction, partial purification and methylation with diazomethane, followed by gas-liquid chromatography. With this technique only trace amounts of isethionic acid were detected in rat heart (0.1 mg/lOOg wet weight tissue) and rat brain (0.2 mg per 100 mg wet weight tissue) and none was detected in dog hearts. Recovery of added isethionic acid was between 95 and 100%. The assay was validated using a sample of squid axoplasm. We were also unable to show ¹⁴C-taurine conversion to ¹⁴C-isethionic acid in rat heart slices. Theories on the mode of action of taurine involving bioconversion to isethionic acid were therefore questioned.
Some recent work suggested that taurine affects
calcium kinetics in perfused guinea-pig hearts and calcium
transport in rat skeletal muscle sarcoplasmic reticulum.
We have investigated the effect of taurine on ATP-dependent
calcium binding and oxalate-dependent calcium uptake in crude
preparations of guinea-pig sarcolemma and in microsomal
preparations enriched in sarcoplasmic reticulum. Taurine
(5-50 mM) was found to have no significant effect on either
ATP-dependent Ca²⁺ binding or uptake in both preparations. This result was observed at all calcium concentrations tested (0.5-100 uM) and at all incubation times used (30 seconds to 20 minutes). Taurine (20 mM) neither altered the effect of cyclic AMP-dependent protein kinase on oxalate-dependent calcium uptake nor exerted a stabilization action on calcium transport in these systems.
In a further attempt to determine the possible physiological role of taurine in mammalian tissues, we have investigated the effect of taurine on passive transport of sodium, potassium and calcium in synaptosomal preparations of rat brain. Taurine, in a dose dependent manner, was found to have an inhibitory effect on both calcium- uptake and release in these preparations. Amino acids structurally similar to taurine ( β- alanine, homotaurine, hypotaurine and ɣ- aminobutyric acid) were also shown to inhibit calcium uptake in these preparations while a - alanine, proline and valine had no significant effect. Taurine (20 mM), though, did not alter the permeability of these preparations to either sodium or potassium. It thus appeared that taurine, and chemically related amino acids, can specifically alter calcium movements in these preparations. It is suggested that this effect is due to the binding of these agents to taurine receptor sites postulated to be present in these membranes. These observations may help to provide an insight into the physiological and pharmacological effects of taurine reported in cardiac and nervous tissues. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate
Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/21967 |
Date | January 1979 |
Creators | Remtulla, Mohamed Akberali |
Source Sets | University of British Columbia |
Language | English |
Detected Language | English |
Type | Text, Thesis/Dissertation |
Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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