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577 results on '"Inoue, Ryuji"'

103. Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl−/water secretion that involves cAMP-dependent activation of CFTR.

Author

Numata, Tomohiro, Sato-Numata, Kaori, Okada, Yasunobu, and Inoue, Ryuji

Abstract

Constipation is a common symptom frequently compromising the quality of daily life. Several mechanistically different drugs have been used to mitigate constipation, including Japanese herbal (Kampo) medicines. However, the mechanisms of their actions are often not well understood. Here we aimed to investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a Kampo medicine empirically prescribed for chronic constipation. Cl− channel activity was measured by the patch-clamp method in human cystic fibrosis transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human intestinal Caco-2 cells. cAMP was measured by a luciferase-based assay. Cell volume change was measured by a particle-sizing and particle-counting analyzer and video-microscopic measurement. In both CFTR-expressing HEK293T and Caco-2 cells, JCT dose-dependently induced whole-cell currents showing typical biophysical and pharmacological features of CFTR. Robust expression of CFTR was confirmed by RT-PCR and Western blotting in Caco-2 cells. Luciferase-based measurement revealed that JCT increases intracellular cAMP levels. Administration of the adenylate cyclase inhibitor SQ22536 or CFTR inhibitor-172, or treatment with small interfering RNAs (siRNA) targeting CFTR, abolished JCT-induced whole-cell currents, suggesting that elevated intracellular cAMP by JCT causes activation of CFTR in Caco-2 cells. Finally, blockade of CFTR activity by CFTR inhibitor-172 or siRNA-knockdown of CFTR or application of SQ22536 markedly reduced the degree of cell volume decrease induced by JCT. JCT can induce a Cl− efflux through the CFTR channel to promote water secretion, and this effect is likely mediated by increased cAMP production. [ABSTRACT FROM AUTHOR]

Published
2018
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104. Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAAReceptor Using a Turn-On Probe

Author

Sakamoto, Seiji, Yamaura, Kei, Numata, Tomohiro, Harada, Fumio, Amaike, Kazuma, Inoue, Ryuji, Kiyonaka, Shigeki, and Hamachi, Itaru

Abstract

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The fast inhibitory actions of GABA are mainly mediated by GABAAreceptors (GABAARs), which are widely recognized as clinically relevant drug targets. However, it remains difficult to create screening systems for drug candidates that act on GABAARs because of the existence of multiple ligand-binding sites and the delicate pentameric structures of GABAARs. We here developed the first turn-on fluorescent imaging probe for GABAARs, which can be used to quantitatively evaluate ligand–receptor interactions under live cell conditions. Using noncovalent labeling of GABAARs with this turn-on probe, a new imaging-based ligand assay system, which allows discovery of positive allosteric modulators (PAMs) for the GABAAR, was successfully constructed. Our system is applicable to high-throughput ligand screening, and we discovered new small molecules that function as PAMs for GABAARs. These results highlight the power of the use of a turn-on fluorescent probe to screen drugs for complicated membrane proteins that cannot be addressed by conventional methods.

Published
2019
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106. Strategy to Attain Remarkably High Photoinduced Charge-Separation Yield of Donor–Acceptor Linked Molecules in Biological Environment via Modulating Their Cationic Moieties

Author

Cai, Ning, Takano, Yuta, Numata, Tomohiro, Inoue, Ryuji, Mori, Yasuo, Murakami, Tatsuya, and Imahori, Hiroshi

Abstract

A series of ferrocene–porphyrin–fullerene linked triads (TC1, TC2, and TC4) possessing different numbers of cationic moieties were designed and prepared to achieve a high photoinduced charge-separation (CS) yield in a biological environment. In a solution, TC1, TC2, and TC4demonstrated the formation of their nanoaggregates. Among the new triads, TC4possessing the four cationic moieties exhibited the formation of a long-lived charge-separated state with the highest CS yield (86%) ever reported in cell membrane-like lipid bilayers, which is consistent with the largest change in the cell membrane potential of PC12 cells via the photoinduced CS under green light illumination. The highest CS yield in the biological environment can be rationalized by the well-tailored balance in hydrophobicity and hydrophilicity of TC4. This finding provides a strategy to improve greatly the photoinduced charge-separation yield of donor–acceptor linked molecules in the biological environment and also will be informative for extracting the full potential of the photoinduced charge-separated state toward biological applications.

Published
2024
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107. Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds

Author

Sawamura, Seishiro, primary, Hatano, Masahiko, additional, Takada, Yoshinori, additional, Hino, Kyosuke, additional, Kawamura, Tetsuya, additional, Tanikawa, Jun, additional, Nakagawa, Hiroshi, additional, Hase, Hideharu, additional, Nakao, Akito, additional, Hirano, Mitsuru, additional, Rotrattanadumrong, Rachapun, additional, Kiyonaka, Shigeki, additional, Mori, Masayuki X., additional, Nishida, Motohiro, additional, Hu, Yaopeng, additional, Inoue, Ryuji, additional, Nagata, Ryu, additional, and Mori, Yasuo, additional

Published
2016
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112. Optical control of neuronal firing via photoinduced electron transfer in donor–acceptor conjugates

Author

Takano, Yuta, primary, Numata, Tomohiro, additional, Fujishima, Kazuto, additional, Miyake, Kazuaki, additional, Nakao, Kazuya, additional, Grove, Wesley David, additional, Inoue, Ryuji, additional, Kengaku, Mineko, additional, Sakaki, Shigeyoshi, additional, Mori, Yasuo, additional, Murakami, Tatsuya, additional, and Imahori, Hiroshi, additional

Published
2016
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113. Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway.

Author

80212265, Mori, Masayuki X, Itsuki, Kyohei, Hase, Hideharu, Sawamura, Seishiro, Kurokawa, Tatsuki, Mori, Yasuo, Inoue, Ryuji, 80212265, Mori, Masayuki X, Itsuki, Kyohei, Hase, Hideharu, Sawamura, Seishiro, Kurokawa, Tatsuki, Mori, Yasuo, and Inoue, Ryuji

Abstract

Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable, nonselective cation channels that carry receptor-operated Ca(2+) currents (ROCs) triggered by receptor-induced, phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4, 5-bisphosphate [PI(4, 5)P2]. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction, and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4, 5)P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4, 5)P2 and the possible role of PI(4, 5)P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4, 5)P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4, 5)P2 using a model simulation that could explain the complicated effects of PI(4, 5)P2 on different ROCs.

Published
2015

116. Cardiac Natriuretic Peptides Inhibit TRPC6-Mediated Prohypertrophic Signaling

Author

Kinoshita, Hideyuki, Koichiro Kuwahara, Inoue, Ryuji, Nishida, Motohiro, Kurose, Hitoshi, Kiyonaka, Shigeki, Mori, Yasuo, Harada, Masaki, Murakami, Masao, Nakagawa, Yasuaki, Yasuno, Shinji, Usami, Satoru, Fujiwara, Masataka, Kuwabara, Yoshihiro, Minami, Takeya, Yamada, Yuko, Ueshima, Kenji, and Nakao, Kazuwa

Published
2009

121. Atrial and brain natriuretic peptides-guanylyl cyclase-A signaling pathway inhibits TRPC6-mediated pro-hypertrophic signaling in the hearts

Author

Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jiang, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Ueshima, Kenji, Nakao, Kazuwa, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jiang, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Ueshima, Kenji, and Nakao, Kazuwa

Published
2010

122. Inhibition of TRPC6 Channel Activity Contributes to the Antihypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart

Author

Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jian, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Fujiwara, Masataka, Yamada, Yuko, Minami, Takeya, Ueshima, Kenji, Nakao, Kazuwa, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jian, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Fujiwara, Masataka, Yamada, Yuko, Minami, Takeya, Ueshima, Kenji, and Nakao, Kazuwa

Published
2010

123. Atrial and brain natriuretic peptides-guanylyl cyclase-A signaling pathway inhibits TRPC6-mediated pro-hypertrophic signaling in the hearts

Author

80212265, 70452357, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jiang, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Ueshima, Kenji, Nakao, Kazuwa, 80212265, 70452357, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jiang, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Ueshima, Kenji, and Nakao, Kazuwa

Published
2010

124. Ca2+ influx and protein scaffolding via TRPC3 sustain PKC beta and ERK activation in B cells

Author

90422980, 60228715, 80212265, Numaga, Takuro, Nishida, Motohiro, Kiyonaka, Shigeki, Kato, Kenta, Katano, Masahiro, Mori, Emiko, Kurosaki, Tomohiro, Inoue, Ryuji, Hikida, Masaki, Putney Jr., James W., Mori, Yasuo, 90422980, 60228715, 80212265, Numaga, Takuro, Nishida, Motohiro, Kiyonaka, Shigeki, Kato, Kenta, Katano, Masahiro, Mori, Emiko, Kurosaki, Tomohiro, Inoue, Ryuji, Hikida, Masaki, Putney Jr., James W., and Mori, Yasuo

Published
2010

125. Inhibition of TRPC6 Channel Activity Contributes to the Antihypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart

Author

30467477, 30402887, 90422980, 80212265, 70452357, 40213334, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jian, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Fujiwara, Masataka, Yamada, Yuko, Minami, Takeya, Ueshima, Kenji, Nakao, Kazuwa, 30467477, 30402887, 90422980, 80212265, 70452357, 40213334, Kinoshita, Hideyuki, Kuwahara, Koichiro, Nishida, Motohiro, Jian, Zhong, Rong, Xianglu, Kiyonaka, Shigeki, Kuwabara, Yoshihiro, Kurose, Hitoshi, Inoue, Ryuji, Mori, Yasuo, Li, Yuhao, Nakagawa, Yasuaki, Usami, Satoru, Fujiwara, Masataka, Yamada, Yuko, Minami, Takeya, Ueshima, Kenji, and Nakao, Kazuwa

Published
2010

128. Sympathetic regulation of arterial tonus via TRPC3/NCX1 coupling

Author

Kita, Satomi, Yoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, Iwamoto, Takahiro, Kita, Satomi, Yoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, and Iwamoto, Takahiro

Published
2009

129. REGULATION OF ARTERIAL TONE BY TRPC3/NCX1 COUPLING

Author

Kita, Satomi, Iyoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, Iwamoto, Takahiro, Kita, Satomi, Iyoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, and Iwamoto, Takahiro

Published
2009

132. The Role of L- and T-Type Calcium Channels in Local and Remote Calcium Responses in Rat Mesenteric Terminal Arterioles

Author

Braunstein, Thomas Hartig, Inoue, Ryuji, Cribbs, Leanne, Oike, Masahiro, Ito, Yushi, von Holstein-Rathlou, Niels-Henrik, Jensen, Lars Jørn, Braunstein, Thomas Hartig, Inoue, Ryuji, Cribbs, Leanne, Oike, Masahiro, Ito, Yushi, von Holstein-Rathlou, Niels-Henrik, and Jensen, Lars Jørn

Abstract

Udgivelsesdato: 2008-Sep-2, Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca(2+) channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca(2+) imaging (R) using Fura-PE3 with micro-ejection of depolarizing KCl solution and VDCC blockers, and immunohistochemical and RT-PCR techniques were applied to isolated rat mesenteric terminal arterioles (n = 71 from 47 rats; intraluminal diameter: 24 +/- 1 mum; length: 550-700 mum). Results: Local application of KCl (at 0 mum) led to local (DeltaR = 0.54) and remote (DeltaR = 0.17 at 500 mum) increases in intracellular Ca(2+). Remote Ca(2+) responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. Ca(V)1.2, Ca(V)3.1 and Ca(V)3.2 channels were immunolocalized in vascular smooth muscle cells and Ca(V)3.2 in adjacent endothelial cells. Local and remote Ca(2+) responses were inhibited by bath application of L- and T-type blockers [nifedipine, NNC 55-0396 and R(-)-efonidipine]. Remote Ca(2+) responses (500 mum) were not affected by abolishing Ca(2+) entry at an intermediate position on the arterioles (at 200-300 mum) using micro-application of VDCC blockers. Conclusion: Both L- and T-type channels mediate Ca(2+) entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se.

Published
2009

135. REGULATION OF ARTERIAL TONE BY TRPC3/NCX1 COUPLING

Author

80212265, Kita, Satomi, Iyoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, Iwamoto, Takahiro, 80212265, Kita, Satomi, Iyoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, and Iwamoto, Takahiro

Published
2009

137. Sympathetic regulation of arterial tonus via TRPC3/NCX1 coupling

Author

90422980, 80212265, Kita, Satomi, Yoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, Iwamoto, Takahiro, 90422980, 80212265, Kita, Satomi, Yoda, Takuya, Arai, Yuji, Komuro, Issei, Inoue, Ryuji, Kato, Kenta, Kiyonaka, Shigeki, Mori, Yasuo, and Iwamoto, Takahiro

Published
2009

138. Cardiac Natriuretic Peptides Inhibit TRPC6-Mediated Prohypertrophic Signaling

Author

90422980, 80212265, 70452357, Kinoshita, Hideyuki, Kuwahara, Koichiro, Inoue, Ryuji, Nishida, Motohiro, Kurose, Hitoshi, Kiyonaka, Shigeki, Mori, Yasuo, Harada, Masaki, Murakami, Masao, Nakagawa, Yasuaki, Yasuno, Shinji, Usami, Satoru, Fujiwara, Masataka, Kuwabara, Yoshihiro, Minami, Takeya, Yamada, Yuko, Ueshima, Kenji, Nakao, Kazuwa, 90422980, 80212265, 70452357, Kinoshita, Hideyuki, Kuwahara, Koichiro, Inoue, Ryuji, Nishida, Motohiro, Kurose, Hitoshi, Kiyonaka, Shigeki, Mori, Yasuo, Harada, Masaki, Murakami, Masao, Nakagawa, Yasuaki, Yasuno, Shinji, Usami, Satoru, Fujiwara, Masataka, Kuwabara, Yoshihiro, Minami, Takeya, Yamada, Yuko, Ueshima, Kenji, and Nakao, Kazuwa

Published
2009

139. Synergistic Activation of Vascular TRPC6 Channel by Receptor and Mechanical Stimulation via Phospholipase C/Diacylglycerol and Phospholipase A(2)/omega-Hydroxylase/20-HETE Pathways

Author

80342640, 80212265, Inoue, Ryuji, Jensen, Lars J., Jian, Zhong, Shi, Juan, Hai, Lin, Lurie, Andrew I., Henriksen, Freja H., Salomonsson, Max, Morita, Hiromitsu, Kawarabayashi, Yasuhiro, Mori, Masayuki, Mori, Yasuo, Ito, Yushi, 80342640, 80212265, Inoue, Ryuji, Jensen, Lars J., Jian, Zhong, Shi, Juan, Hai, Lin, Lurie, Andrew I., Henriksen, Freja H., Salomonsson, Max, Morita, Hiromitsu, Kawarabayashi, Yasuhiro, Mori, Masayuki, Mori, Yasuo, and Ito, Yushi

Published
2009

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