title: Vasorelaxant Effect of 5'-Methylthioadenosine Obtained from Candida utilis Yeast Extract through the Suppression of Intracellular Ca(2+) Concentration in Isolated Rat Aorta.
abstract: 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.
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University , 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Thanutchaporn
authors.initials: T
authors.lastname: Kumrungsee
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University , 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Akiyama
authors.affiliation: KOHJIN Life Sciences Company Ltd. , Saiki-Factory, 1-6 Higashihama, Saiki-shi, Oita 876-8580, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Saiki
authors.affiliation: KOHJIN Life Sciences Company Ltd. , Saiki-Factory, 1-6 Higashihama, Saiki-shi, Oita 876-8580, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Omae
authors.affiliation: KOHJIN Life Sciences Company Ltd. , Saiki-Factory, 1-6 Higashihama, Saiki-shi, Oita 876-8580, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hamasawa
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University , 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002175:Candida / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013872:Thionucleosides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D003839:Deoxyadenosines; D013872:Thionucleosides; D014665:Vasodilator Agents; C008500:5'-methylthioadenosine; D002118:Calcium
keywords: 5′-methylthioadenosine; Ca2+ channel; calmodulin-dependent kinase II; vasorelaxation; yeast extract