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

摘要

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, S'-methylthioadenosine (MTA) exhibited comparable vasorelaxant effect (EC50 of 190 +/- 40 mu M) with adenosine, a known vasodilator, on 1 mu M 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 mu M 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.