Vasorelaxant Effect of 5′-Methylthioadenosine Obtained from Candida utilis Yeast Extract through the Suppression of Intracellular Ca²⁺ Concentration in Isolated Rat Aorta

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Our study is the first to demonstrate the vasorelaxant effect of Candida utilis yeast extract on rat aorta (EC₅₀ of 7.2 ± 3.2 mg/mL). Among five identified compounds, 5′-methylthioadenosine (MTA) exhibited comparable vasorelaxant effect (EC₅₀ of 190 ± 40 μM) with adenosine, a known vasodilator, on 1 μM phenylephrine (PE)-contracted Sprague–Dawley rat aortic rings. MTA induced vasorelaxation in an endothelium-independent manner and independent of the adenosine receptors. MTA reduced a CaCl₂-induced vasocontraction stimulated by 1 μM PE, whereas the effect was abolished in a 60 mM KCl-induced vasocontraction. This indicates that MTA was not involved in the suppression of extracellular Ca²⁺ influx. MTA significantly (P < 0.01) attenuated the PE-induced activation of calmodulin-dependent kinase II (CaMK II) in aortic rings and inhibited the phosphorylation of L-type Ca²⁺ channel (VDCC). In conclusion, the underlying mechanism(s) of MTA-induced vasorelaxation involves the inhibition of Ca²⁺/CaMK II/VDCC phosphorylation pathway, resulting in the suppression of intracellular Ca²⁺ concentration in aortic rings.