Vasorelaxant Effect of 5'-Methylthioadenosine Obtained from Candida utilis Yeast Extract through the Suppression of Intracellular Ca(2+) Concentration in Isolated Rat Aorta

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,...

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Published in:Journal of agricultural and food chemistry 2016-05, Vol.64 (17), p.3362-3370
Main Authors: Kumrungsee, Thanutchaporn, Akiyama, Sayaka, Saiki, Tomomi, Omae, Masato, Hamasawa, Kazuhiro, Matsui, Toshiro
Format: Article
Language:English
Subjects:
Animals
Aorta - drug effects
Aorta - metabolism
Calcium - metabolism
Candida - chemistry
Chromatography, High Pressure Liquid
Deoxyadenosines - pharmacology
In Vitro Techniques
Male
Mass Spectrometry
Rats
Rats, Sprague-Dawley
Thionucleosides - pharmacology
Vasodilator Agents - pharmacology
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Summary: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 Ca(2+) 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 Ca(2+) channel (VDCC). In conclusion, the underlying mechanism(s) of MTA-induced vasorelaxation involves the inhibition of Ca(2+)/CaMK II/VDCC phosphorylation pathway, resulting in the suppression of intracellular Ca(2+) concentration in aortic rings.
ISSN:1520-5118
DOI:10.1021/acs.jafc.6b00679