Takashi Nakamura1, Yasuhiro Shimada1,2, Tomoya Takeda1, Katsuyuki Sato1, Mitsuo Akiba3, Haruhiko Fukaya3. 1. Asai Germanium Research Institute Co., Ltd. Suzuranoka, Hakodate, Hokkaido 042-0958, Japan. 2. The United Graduate School of Agricultural Science, Iwate University, Morioka, Iwate 020-8550, Japan. 3. Tokyo University of Pharmacy & Life Sciences, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Abstract
BACKGROUND: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.
BACKGROUND: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.