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Nobuyuki Yanagihara - One of the best experts on this subject based on the ideXlab platform.
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stimulatory effect of nobiletin a citrus polymethoxy flavone on Catecholamine Synthesis through ser19 and ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells
Naunyn-schmiedebergs Archives of Pharmacology, 2014Co-Authors: Han Zhang, Yumiko Toyohira, Masato Tsutsui, Nobuyuki Yanagihara, Keita Takahashi, Hirohide Inagaki, Noriaki Satoh, Xiaoja Li, Kojiro TakahaishiAbstract:We previously reported the dual effects of nobiletin, a compound of polymethoxy flavones found in citrus fruits, on Catecholamine secretion in cultured bovine adrenal medullary cells. Here, we report the effects of nobiletin on Catecholamine Synthesis in the cells. Nobiletin increased the Synthesis of 14C-Catecholamines from [14C]tyrosine in a time (20–30 min)- and concentration (1.0–100 μM)-dependent manner. Nobiletin (10–100 μM) also activated tyrosine hydroxylase activity. The stimulatory effect of nobiletin on 14C-Catecholamine Synthesis was not observed when extracellular Ca2+ was not present in the incubation medium. Protein kinase inhibitors including H-89, an inhibitor of cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, suppressed the stimulatory effects of nobiletin on Catecholamine Synthesis as well as tyrosine hydroxylase activity. Nobiletin also induced the phosphorylation of tyrosine hydroxylase at Ser19 and Ser40. Nobiletin (1.0–100 μM) inhibited 14C-Catecholamine Synthesis induced by acetylcholine. The present findings suggest that nobiletin, by itself, stimulates Catecholamine Synthesis through tyrosine hydroxylase phosphorylation at Ser19 and Ser40, whereas it inhibits Catecholamine Synthesis induced by acetylcholine in bovine adrenal medulla.
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effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Journal of Pharmacological Sciences, 2014Co-Authors: Hirohide Inagaki, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Keita Takahashi, Go Obara, Toshinori Kawagoe, Toru Hachisuga, Nobuyuki YanagiharaAbstract:Abstract. We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in these cells. Raloxifene caused dual effects on the specific binding of [ 3 H]17 β -estradiol to the plasma membranes isolated from bovine adrenal medulla; that is, it had a stimulatory effect at 1.0 – 10 nM but an inhibitory effect at 1.0 – 10 μ M, whereas tamoxifen (1.0 nM – 10 μ M) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal 14 C-Catecholamine Synthesis from [ 14 C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced 14 C-Catecholamine Synthesis. Raloxifene (0.3, 1.0, and 3 – 100 μ M) and tamoxifen (10 – 100 μ M) also suppressed Catecholamine secretion and 45 Ca 2+ and 22 Na + influx, respectively, induced by acetylcholine. Raloxifene (1.0 μ M) inhibited Na + current evoked by acetylcholine in Xenopus oocytes expressing α 4 β 2 neuronal nicotinic acetylcholine receptors. The present findings suggest that raloxifene and tamoxifen at low concentrations allosterically modulate plasma membrane estrogen receptors and at high concentrations inhibit acetylcholine-induced Catecholamine Synthesis and secretion by inhibiting Na + and Ca 2+ influx in bovine adrenal medulla.
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stimulation of Catecholamine Synthesis in cultured bovine adrenal medullary cells by leptin
Journal of Neurochemistry, 2008Co-Authors: Kensuke Utsunomiya, Yumiko Toyohira, Susumu Ueno, Tat Beng Cheah, Nobuyuki Yanagihara, Eiichi Tachikawa, Koji Kajiwara, Futoshi IzumiAbstract:Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on Catecholamine Synthesis in the cells. Incubating cells with leptin (10 nm) for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine, but not from l-3,4-dihydroxyphenyl [3–14C]alanine. The stimulation of Catecholamine Synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of Catecholamine bioSynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the Synthesis of 14C-Catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-Catecholamine Synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates Catecholamine Synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.
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dual effects of daidzein a soy isoflavone on Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Endocrinology, 2007Co-Authors: Nobuyuki Yanagihara, Yumiko Toyohira, Masato Tsutsui, Susume Ueno, Yuko ShinoharaAbstract:We recently demonstrated the occurrence and functional roles of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of daidzein, a phytoestrogen of soybeans, on Catecholamine Synthesis and secretion in the cells. Incubation of cells with daidzein for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine but not [14C]dihydroxyphenylalanine, in a concentration-dependent manner (10–1000 nm). The stimulatory effect of daidzein on 14C-Catecholamine Synthesis was not inhibited by ICI182,780, a classical estrogen receptor inhibitor. Acetylcholine, a physiological secretagogue, stimulated the Synthesis of 14C-Catecholamines, which was suppressed by daidzein at 1 μm. Daidzein at high concentrations (1–100 μm) suppressed Catecholamine secretion induced by acetylcholine. Furthermore, daidzein (10–1000 nm) inhibited the specific binding of [3H]17β-estradiol to plasma membranes isolated from bovine adrenal medulla. The present findings suggest tha...
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stimulation of Catecholamine Synthesis via activation of p44 42 mapk in cultured bovine adrenal medullary cells by milnacipran
Naunyn-schmiedebergs Archives of Pharmacology, 2007Co-Authors: Koji Shinkai, Yumiko Toyohira, Masato Tsutsui, Reiji Yoshimura, Susume Ueno, Jun Nakamura, Nobuyuki YanagiharaAbstract:Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used clinically as an antidepressant. We report here the effect of milnacipran on Catecholamine Synthesis in cultured bovine adrenal medullary cells. Incubation of adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min resulted in a significant increase in 14C-Catecholamine Synthesis from [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml, 691 nM), had little effect. Milnacipran, but not paroxetine or fluvoxamine, increased the activity of tyrosine hydroxylase, the rate-limiting step of Catecholamine bioSynthesis, in a concentration-dependent manner (100–300 ng/ml, 355–1,065 nM). U0126 (1 μM), an inhibitor of p44/42 mitogen-activated protein kinase (MAPK) kinase, abolished the stimulatory effects of milnacipran on tyrosine hydroxylase activity. Furthermore, incubation of cells with milnacipran (30–100 ng/ml) for 5 min activated p44/42 MAPK, whereas paroxetine and fluvoxamine did not. The present findings suggest that milnacipran activates tyrosine hydroxylase and then stimulates Catecholamine Synthesis through a p44/42 MAPK-dependent pathway in cultured bovine adrenal medullary cells.
Masato Tsutsui - One of the best experts on this subject based on the ideXlab platform.
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effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Journal of Pharmacological Sciences, 2014Co-Authors: Hirohide Inagaki, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Keita Takahashi, Go Obara, Toshinori Kawagoe, Toru Hachisuga, Nobuyuki YanagiharaAbstract:Abstract. We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in these cells. Raloxifene caused dual effects on the specific binding of [ 3 H]17 β -estradiol to the plasma membranes isolated from bovine adrenal medulla; that is, it had a stimulatory effect at 1.0 – 10 nM but an inhibitory effect at 1.0 – 10 μ M, whereas tamoxifen (1.0 nM – 10 μ M) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal 14 C-Catecholamine Synthesis from [ 14 C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced 14 C-Catecholamine Synthesis. Raloxifene (0.3, 1.0, and 3 – 100 μ M) and tamoxifen (10 – 100 μ M) also suppressed Catecholamine secretion and 45 Ca 2+ and 22 Na + influx, respectively, induced by acetylcholine. Raloxifene (1.0 μ M) inhibited Na + current evoked by acetylcholine in Xenopus oocytes expressing α 4 β 2 neuronal nicotinic acetylcholine receptors. The present findings suggest that raloxifene and tamoxifen at low concentrations allosterically modulate plasma membrane estrogen receptors and at high concentrations inhibit acetylcholine-induced Catecholamine Synthesis and secretion by inhibiting Na + and Ca 2+ influx in bovine adrenal medulla.
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stimulatory effect of nobiletin a citrus polymethoxy flavone on Catecholamine Synthesis through ser19 and ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells
Naunyn-schmiedebergs Archives of Pharmacology, 2014Co-Authors: Han Zhang, Yumiko Toyohira, Masato Tsutsui, Nobuyuki Yanagihara, Keita Takahashi, Hirohide Inagaki, Noriaki Satoh, Xiaoja Li, Kojiro TakahaishiAbstract:We previously reported the dual effects of nobiletin, a compound of polymethoxy flavones found in citrus fruits, on Catecholamine secretion in cultured bovine adrenal medullary cells. Here, we report the effects of nobiletin on Catecholamine Synthesis in the cells. Nobiletin increased the Synthesis of 14C-Catecholamines from [14C]tyrosine in a time (20–30 min)- and concentration (1.0–100 μM)-dependent manner. Nobiletin (10–100 μM) also activated tyrosine hydroxylase activity. The stimulatory effect of nobiletin on 14C-Catecholamine Synthesis was not observed when extracellular Ca2+ was not present in the incubation medium. Protein kinase inhibitors including H-89, an inhibitor of cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, suppressed the stimulatory effects of nobiletin on Catecholamine Synthesis as well as tyrosine hydroxylase activity. Nobiletin also induced the phosphorylation of tyrosine hydroxylase at Ser19 and Ser40. Nobiletin (1.0–100 μM) inhibited 14C-Catecholamine Synthesis induced by acetylcholine. The present findings suggest that nobiletin, by itself, stimulates Catecholamine Synthesis through tyrosine hydroxylase phosphorylation at Ser19 and Ser40, whereas it inhibits Catecholamine Synthesis induced by acetylcholine in bovine adrenal medulla.
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dual effects of daidzein a soy isoflavone on Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Endocrinology, 2007Co-Authors: Nobuyuki Yanagihara, Yumiko Toyohira, Masato Tsutsui, Susume Ueno, Yuko ShinoharaAbstract:We recently demonstrated the occurrence and functional roles of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of daidzein, a phytoestrogen of soybeans, on Catecholamine Synthesis and secretion in the cells. Incubation of cells with daidzein for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine but not [14C]dihydroxyphenylalanine, in a concentration-dependent manner (10–1000 nm). The stimulatory effect of daidzein on 14C-Catecholamine Synthesis was not inhibited by ICI182,780, a classical estrogen receptor inhibitor. Acetylcholine, a physiological secretagogue, stimulated the Synthesis of 14C-Catecholamines, which was suppressed by daidzein at 1 μm. Daidzein at high concentrations (1–100 μm) suppressed Catecholamine secretion induced by acetylcholine. Furthermore, daidzein (10–1000 nm) inhibited the specific binding of [3H]17β-estradiol to plasma membranes isolated from bovine adrenal medulla. The present findings suggest tha...
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stimulation of Catecholamine Synthesis via activation of p44 42 mapk in cultured bovine adrenal medullary cells by milnacipran
Naunyn-schmiedebergs Archives of Pharmacology, 2007Co-Authors: Koji Shinkai, Yumiko Toyohira, Masato Tsutsui, Reiji Yoshimura, Susume Ueno, Jun Nakamura, Nobuyuki YanagiharaAbstract:Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used clinically as an antidepressant. We report here the effect of milnacipran on Catecholamine Synthesis in cultured bovine adrenal medullary cells. Incubation of adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min resulted in a significant increase in 14C-Catecholamine Synthesis from [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml, 691 nM), had little effect. Milnacipran, but not paroxetine or fluvoxamine, increased the activity of tyrosine hydroxylase, the rate-limiting step of Catecholamine bioSynthesis, in a concentration-dependent manner (100–300 ng/ml, 355–1,065 nM). U0126 (1 μM), an inhibitor of p44/42 mitogen-activated protein kinase (MAPK) kinase, abolished the stimulatory effects of milnacipran on tyrosine hydroxylase activity. Furthermore, incubation of cells with milnacipran (30–100 ng/ml) for 5 min activated p44/42 MAPK, whereas paroxetine and fluvoxamine did not. The present findings suggest that milnacipran activates tyrosine hydroxylase and then stimulates Catecholamine Synthesis through a p44/42 MAPK-dependent pathway in cultured bovine adrenal medullary cells.
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Stimulation of Catecholamine Synthesis via activation of p44/42 MAPK in cultured bovine adrenal medullary cells by milnacipran
Naunyn-schmiedebergs Archives of Pharmacology, 2007Co-Authors: Koji Shinkai, Yumiko Toyohira, Masato Tsutsui, Reiji Yoshimura, Susume Ueno, Jun Nakamura, Nobuyuki YanagiharaAbstract:Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used clinically as an antidepressant. We report here the effect of milnacipran on Catecholamine Synthesis in cultured bovine adrenal medullary cells. Incubation of adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min resulted in a significant increase in 14C-Catecholamine Synthesis from [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml, 691 nM), had little effect. Milnacipran, but not paroxetine or fluvoxamine, increased the activity of tyrosine hydroxylase, the rate-limiting step of Catecholamine bioSynthesis, in a concentration-dependent manner (100–300 ng/ml, 355–1,065 nM). U0126 (1 μM), an inhibitor of p44/42 mitogen-activated protein kinase (MAPK) kinase, abolished the stimulatory effects of milnacipran on tyrosine hydroxylase activity. Furthermore, incubation of cells with milnacipran (30–100 ng/ml) for 5 min activated p44/42 MAPK, whereas paroxetine and fluvoxamine did not. The present findings suggest that milnacipran activates tyrosine hydroxylase and then stimulates Catecholamine Synthesis through a p44/42 MAPK-dependent pathway in cultured bovine adrenal medullary cells.
Yumiko Toyohira - One of the best experts on this subject based on the ideXlab platform.
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stimulatory effect of nobiletin a citrus polymethoxy flavone on Catecholamine Synthesis through ser19 and ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells
Naunyn-schmiedebergs Archives of Pharmacology, 2014Co-Authors: Han Zhang, Yumiko Toyohira, Masato Tsutsui, Nobuyuki Yanagihara, Keita Takahashi, Hirohide Inagaki, Noriaki Satoh, Xiaoja Li, Kojiro TakahaishiAbstract:We previously reported the dual effects of nobiletin, a compound of polymethoxy flavones found in citrus fruits, on Catecholamine secretion in cultured bovine adrenal medullary cells. Here, we report the effects of nobiletin on Catecholamine Synthesis in the cells. Nobiletin increased the Synthesis of 14C-Catecholamines from [14C]tyrosine in a time (20–30 min)- and concentration (1.0–100 μM)-dependent manner. Nobiletin (10–100 μM) also activated tyrosine hydroxylase activity. The stimulatory effect of nobiletin on 14C-Catecholamine Synthesis was not observed when extracellular Ca2+ was not present in the incubation medium. Protein kinase inhibitors including H-89, an inhibitor of cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, suppressed the stimulatory effects of nobiletin on Catecholamine Synthesis as well as tyrosine hydroxylase activity. Nobiletin also induced the phosphorylation of tyrosine hydroxylase at Ser19 and Ser40. Nobiletin (1.0–100 μM) inhibited 14C-Catecholamine Synthesis induced by acetylcholine. The present findings suggest that nobiletin, by itself, stimulates Catecholamine Synthesis through tyrosine hydroxylase phosphorylation at Ser19 and Ser40, whereas it inhibits Catecholamine Synthesis induced by acetylcholine in bovine adrenal medulla.
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effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Journal of Pharmacological Sciences, 2014Co-Authors: Hirohide Inagaki, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Keita Takahashi, Go Obara, Toshinori Kawagoe, Toru Hachisuga, Nobuyuki YanagiharaAbstract:Abstract. We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in these cells. Raloxifene caused dual effects on the specific binding of [ 3 H]17 β -estradiol to the plasma membranes isolated from bovine adrenal medulla; that is, it had a stimulatory effect at 1.0 – 10 nM but an inhibitory effect at 1.0 – 10 μ M, whereas tamoxifen (1.0 nM – 10 μ M) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal 14 C-Catecholamine Synthesis from [ 14 C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced 14 C-Catecholamine Synthesis. Raloxifene (0.3, 1.0, and 3 – 100 μ M) and tamoxifen (10 – 100 μ M) also suppressed Catecholamine secretion and 45 Ca 2+ and 22 Na + influx, respectively, induced by acetylcholine. Raloxifene (1.0 μ M) inhibited Na + current evoked by acetylcholine in Xenopus oocytes expressing α 4 β 2 neuronal nicotinic acetylcholine receptors. The present findings suggest that raloxifene and tamoxifen at low concentrations allosterically modulate plasma membrane estrogen receptors and at high concentrations inhibit acetylcholine-induced Catecholamine Synthesis and secretion by inhibiting Na + and Ca 2+ influx in bovine adrenal medulla.
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stimulation of Catecholamine Synthesis in cultured bovine adrenal medullary cells by leptin
Journal of Neurochemistry, 2008Co-Authors: Kensuke Utsunomiya, Yumiko Toyohira, Susumu Ueno, Tat Beng Cheah, Nobuyuki Yanagihara, Eiichi Tachikawa, Koji Kajiwara, Futoshi IzumiAbstract:Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on Catecholamine Synthesis in the cells. Incubating cells with leptin (10 nm) for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine, but not from l-3,4-dihydroxyphenyl [3–14C]alanine. The stimulation of Catecholamine Synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of Catecholamine bioSynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the Synthesis of 14C-Catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-Catecholamine Synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates Catecholamine Synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.
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dual effects of daidzein a soy isoflavone on Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Endocrinology, 2007Co-Authors: Nobuyuki Yanagihara, Yumiko Toyohira, Masato Tsutsui, Susume Ueno, Yuko ShinoharaAbstract:We recently demonstrated the occurrence and functional roles of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of daidzein, a phytoestrogen of soybeans, on Catecholamine Synthesis and secretion in the cells. Incubation of cells with daidzein for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine but not [14C]dihydroxyphenylalanine, in a concentration-dependent manner (10–1000 nm). The stimulatory effect of daidzein on 14C-Catecholamine Synthesis was not inhibited by ICI182,780, a classical estrogen receptor inhibitor. Acetylcholine, a physiological secretagogue, stimulated the Synthesis of 14C-Catecholamines, which was suppressed by daidzein at 1 μm. Daidzein at high concentrations (1–100 μm) suppressed Catecholamine secretion induced by acetylcholine. Furthermore, daidzein (10–1000 nm) inhibited the specific binding of [3H]17β-estradiol to plasma membranes isolated from bovine adrenal medulla. The present findings suggest tha...
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stimulation of Catecholamine Synthesis via activation of p44 42 mapk in cultured bovine adrenal medullary cells by milnacipran
Naunyn-schmiedebergs Archives of Pharmacology, 2007Co-Authors: Koji Shinkai, Yumiko Toyohira, Masato Tsutsui, Reiji Yoshimura, Susume Ueno, Jun Nakamura, Nobuyuki YanagiharaAbstract:Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used clinically as an antidepressant. We report here the effect of milnacipran on Catecholamine Synthesis in cultured bovine adrenal medullary cells. Incubation of adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min resulted in a significant increase in 14C-Catecholamine Synthesis from [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml, 691 nM), had little effect. Milnacipran, but not paroxetine or fluvoxamine, increased the activity of tyrosine hydroxylase, the rate-limiting step of Catecholamine bioSynthesis, in a concentration-dependent manner (100–300 ng/ml, 355–1,065 nM). U0126 (1 μM), an inhibitor of p44/42 mitogen-activated protein kinase (MAPK) kinase, abolished the stimulatory effects of milnacipran on tyrosine hydroxylase activity. Furthermore, incubation of cells with milnacipran (30–100 ng/ml) for 5 min activated p44/42 MAPK, whereas paroxetine and fluvoxamine did not. The present findings suggest that milnacipran activates tyrosine hydroxylase and then stimulates Catecholamine Synthesis through a p44/42 MAPK-dependent pathway in cultured bovine adrenal medullary cells.
Toshiaki Nakai - One of the best experts on this subject based on the ideXlab platform.
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angiotensin ii type 2 receptor counter regulates type 1 receptor in Catecholamine Synthesis in cultured porcine adrenal medullary chromaffin cells
Hypertension, 2002Co-Authors: Kazuhiro Takekoshi, Kiyoaki Ishii, Shunsuke Shibuya, Yasushi Kawakami, Kazumasa Isobe, Toshiaki NakaiAbstract:We previously showed that CGP 42112 (an angiotensin type 2 [AT 2 ] agonist) markedly reduces Catecholamine bioSynthesis by decreasing cGMP production mediated by AT 2 , a subtype of Ang II receptor that is dominantly expressed in cultured porcine chromaffin cells. To elucidate the relationship of the 2 types of Ang II receptors, angiotensin type 1 (AT 1 ) and AT 2 , in the Synthesis of Catecholamine in adrenal medullary cells, we have examined the effect of Ang II plus CV-11974 (an AT 1 antagonist that selectively simulates AT 2 stimulation) and the effect of Ang II plus PD 123319 (an AT 2 antagonist that selectively simulates AT 1 stimulation) on Catecholamine Synthesis. We found that Ang II reduced cGMP production via AT 2 , in a similar manner to that found with CGP 42112. Stimulation of AT 1 significantly upregulated protein kinase C activity. Tyrosine hydroxylase (TH) is a rate-limiting enzyme involved in the bioSynthesis of Catecholamine, and this Catecholamine Synthesis depends both on TH enzyme activity and on the levels of TH protein after TH gene transcription. We found that AT 2 stimulation significantly inhibited TH enzyme activity, whereas AT 1 stimulation significantly upregulated TH enzyme activity. The stimulatory effect of AT 1 was completely inhibited by Ro-32-0432 (a protein kinase C inhibitor) and PD 98059 (a MAP kinase kinase-1 [MEK-1] inhibitor). Pretreatment of cells with either 8-Br-cGMP (a membrane-permeable cGMP analog) or Zaprinast (a phosphodiesterase inhibitor) abolished the inhibitory effect of AT 2 on TH enzyme activity, indicating that the stimulatory effect of AT 2 may be mediated through a reduction in cGMP concentration. Similar to the effect on TH enzyme activity, AT 2 stimulation significantly reduced TH mRNA and protein levels and net Catecholamine content below basal levels, whereas AT 1 stimulation increased them. We confirmed these findings by gel mobility shift assay. Our results show that stimulation of AT 2 reduces Catecholamine bioSynthesis via a decrease in cGMP levels. In contrast, stimulation of AT 1 stimulates Catecholamine bioSynthesis through activation of PKC. Thus, we conclude that AT 1 and AT 2 have counter-regulatory roles in the Synthesis of Catecholamine in adrenal medullary chromaffin cells.
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leptin stimulates Catecholamine Synthesis in a pkc dependent manner in cultured porcine adrenal medullary chromaffin cells
Endocrinology, 2001Co-Authors: Kazuhiro Takekoshi, Kiyoaki Ishii, Toru Nanmoku, Shunsuke Shibuya, Yasushi Kawakami, Kazumasa Isobe, Toshiaki NakaiAbstract:We have previously shown that murine recombinant leptin directly stimulates Catecholamine Synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells. Additionally, we found that leptin activates IP3 production after PLC activation. It is well established that activation of PLC elicits IP3 production as well as an increase in diacylglycerol, a compound that stimulates PKC. Therefore, we investigated the involvement of PKC in leptin-induced Catecholamine Synthesis. Leptin was found to induce significant increases in PKC activity in a dose-dependent manner (1, 10, and 100 nm); chelation of extracellular Ca2+ by EDTA abolished this PKC stimulatory activity. We also confirmed by Western blot analysis that leptin (at 100 nm) induced significant increases in Ca2+-dependent PKCα, -βI, and -γ expression. The activity of the rate-limiting enzyme tyrosine hydroxylase (TH) in the bioSynthesis of Catecholamine is regulated at the transcriptional and posttranscriptiona...
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orexins suppress Catecholamine Synthesis and secretion in cultured pc12 cells
Biochemical and Biophysical Research Communications, 2000Co-Authors: Toru Nanmoku, Kazuhiro Takekoshi, Kiyoaki Ishii, Yasushi Kawakami, Kazumasa Isobe, Takeshi Sakurai, Akihiro Yamanaka, Katsutoshi Goto, Toshiaki NakaiAbstract:Abstract New orexigenic peptides called orexin-A and -B have recently been described in neurons of the lateral hypothalamus and perifornical area. No orexins have been found in adipose tissues or visceral organs, including the adrenal gland. However, expression of the orexin-receptor 2 (OX2R) in the rat adrenal gland has been reported. To test the effects of orexins on peripheral organs, we investigated their effects on Catecholamine Synthesis and secretion in the rat pheochromocytoma cell line PC12. Orexin-A and -B (100 nM) significantly reduced basal and PACAP-induced tyrosine hydroxylase (TH) (the rate-limiting enzyme in the bioSynthesis of Catecholamines) mRNA levels. Orexin-A and -B (100 nM) also significantly inhibited the PACAP-induced increase in the cAMP level, suggesting that the suppressive effect on TH mRNA is mediated, at least in part, by the cAMP/protein kinase A pathway. Furthermore, orexin-A and -B (100 nM) significantly suppressed basal and PACAP-induced dopamine secretion from PC12 cells. Next, we examined whether orexin receptors (OX1R, OX2R) were present in the rat adrenal gland and PC12 cells. In the adrenal glands, OX2R was as strongly expressed as in the hypothalamus, but OX1R was not detected. On the other hand, neither OX1R nor OX2R was expressed in PC12 cells. However, binding assays showed equal binding of orexin-A and -B to PC12 cells, suggesting the existence in these cells of some receptors for orexins. These results indicate that orexins suppress Catecholamine release and Synthesis, and that the inhibitory effect is mediated by the cAMP/protein kinase A pathway.
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effects of natriuretic peptides anp bnp cnp on Catecholamine Synthesis and th mrna levels in pc12 cells
Life Sciences, 2000Co-Authors: Kazuhiro Takekoshi, Kiyoaki Ishii, Kazumasa Isobe, Fumio Nomura, Toru Nammoku, Toshiaki NakaiAbstract:Abstract Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are present in adrenal chromaffin cells and are co-secreted with Catecholamines suggesting that these natriuretic peptides (NPs) may modulate functions of chromaffin cells in an autocrine and/or paracrine manner. Therefore, we investigated the effects of NPs on tyrosine hydroxylase (TH: a rate-limiting enzyme in bioSynthesis of Catecholamine) mRNA in rat pheochromocytoma PC12 cells. It was also determined whether the cyclic GMP/ cGMP-dependent protein kinase ( cGMP PKG ) pathway was involved in theses effects. Finally, we examined the effects of NPs on intracellular Catecholamine content to confirm increase of Catecholamine Synthesis following TH mRNA induction. NPs (0.1 μ M) induced significant increases of the TH mRNA (ANP = BNP > CNP). Also, the effects of NPs on TH mRNA were mimicked by 8-bromo cyclic GMP (1mM) and were blocked by KT5823 (1 μ M) (inhibitor PKG) or LY-83583 (1 μM) (guanylate cyclase inhibitor). Moreover, NPs were shown to induce significant increases of intracellular Catecholamine contents (ANP = BNP > CNP). These findings suggest that NPs induced increases of TH mRNA through cGMP PKG dependent mechanisms, which, in turn, resulted in stimulation of Catecholamine Synthesis in PC 12 cells.
Susumu Ueno - One of the best experts on this subject based on the ideXlab platform.
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effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells
Journal of Pharmacological Sciences, 2014Co-Authors: Hirohide Inagaki, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Keita Takahashi, Go Obara, Toshinori Kawagoe, Toru Hachisuga, Nobuyuki YanagiharaAbstract:Abstract. We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and Catecholamine Synthesis and secretion in these cells. Raloxifene caused dual effects on the specific binding of [ 3 H]17 β -estradiol to the plasma membranes isolated from bovine adrenal medulla; that is, it had a stimulatory effect at 1.0 – 10 nM but an inhibitory effect at 1.0 – 10 μ M, whereas tamoxifen (1.0 nM – 10 μ M) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal 14 C-Catecholamine Synthesis from [ 14 C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced 14 C-Catecholamine Synthesis. Raloxifene (0.3, 1.0, and 3 – 100 μ M) and tamoxifen (10 – 100 μ M) also suppressed Catecholamine secretion and 45 Ca 2+ and 22 Na + influx, respectively, induced by acetylcholine. Raloxifene (1.0 μ M) inhibited Na + current evoked by acetylcholine in Xenopus oocytes expressing α 4 β 2 neuronal nicotinic acetylcholine receptors. The present findings suggest that raloxifene and tamoxifen at low concentrations allosterically modulate plasma membrane estrogen receptors and at high concentrations inhibit acetylcholine-induced Catecholamine Synthesis and secretion by inhibiting Na + and Ca 2+ influx in bovine adrenal medulla.
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stimulation of Catecholamine Synthesis in cultured bovine adrenal medullary cells by leptin
Journal of Neurochemistry, 2008Co-Authors: Kensuke Utsunomiya, Yumiko Toyohira, Susumu Ueno, Tat Beng Cheah, Nobuyuki Yanagihara, Eiichi Tachikawa, Koji Kajiwara, Futoshi IzumiAbstract:Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on Catecholamine Synthesis in the cells. Incubating cells with leptin (10 nm) for 20 min increased the Synthesis of 14C-Catecholamines from [14C]tyrosine, but not from l-3,4-dihydroxyphenyl [3–14C]alanine. The stimulation of Catecholamine Synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of Catecholamine bioSynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the Synthesis of 14C-Catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-Catecholamine Synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates Catecholamine Synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.
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stimulation of Catecholamine Synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17β estradiol
Biochemical and Biophysical Research Communications, 2006Co-Authors: Nobuyuki Yanagihara, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Yuko Shinohara, Kojiro Takahashi, Kazumi TanakaAbstract:Incubation of cultured bovine adrenal medullary cells with 17{beta}-estradiol (E{sub 2}) (0.3-100 nM) or membrane-impermeable E{sub 2}-bovine serum albumin (100 nM) acutely increased {sup 14}C-Catecholamine Synthesis from [{sup 14}C]tyrosine. The stimulatory effect of E{sub 2} was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E{sub 2} also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [{sup 3}H]E{sub 2} with apparent K {sub d}s of 3.2 and 106 nM, and B {sub max}s of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [{sup 3}H]E{sub 2} was most strongly inhibited by E{sub 2} and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E{sub 2} acutely stimulates Catecholamine Synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla.
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stimulation of Catecholamine Synthesis by environmental estrogenic pollutants
Endocrinology, 2005Co-Authors: Nobuyuki Yanagihara, Kensuke Utsunomiya, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Kazumi TanakaAbstract:Environmental estrogenic pollutants are compounds that have been shown to have estrogenic effects on fetal development and reproductive systems. Less attention, however, has been paid to their influence on neuronal functions. We report here the effects of estrogenic pollutants on Catecholamine Synthesis in bovine adrenal medullary cells used as a model system of noradrenergic neurons. Treatment of cultured bovine adrenal medullary cells with p-nonylphenol and bisphenol A at 10 nm for 3 d stimulated [14C]Catecholamine Synthesis from [14C]tyrosine and tyrosine hydroxylase activity, an effect that was not inhibited by ICI 182,780, an antagonist of estrogen receptors. Significant effects of p-nonylphenol on [14C]Catecholamine Synthesis were observed at 0.1 nm, which is 45 times lower than that of the international regulatory standard (4.5 nm), and the maximum effects were around 10–100 nm. The concentrations (0.1–10 nm) used in the present study are similar to the range observed in rivers in the United States...
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stimulation of Catecholamine Synthesis by orexin a in bovine adrenal medullary cells through orexin receptor 1
Biochemical Pharmacology, 2003Co-Authors: Yasusada Kawada, Kensuke Utsunomiya, Yumiko Toyohira, Susumu Ueno, Masato Tsutsui, Kazumi Tanaka, Kohtaro Asayama, Naoya Morisada, Akira Shirahata, Nobuyuki YanagiharaAbstract:Abstract Orexin-A has recently been identified as a new hypothalamic peptide working as a mediator in the regulation of feeding behavior and sleep control. To determine the role of orexin-A in peripheral metabolic processes, we examined direct effects of orexin-A on Catecholamine Synthesis and secretion in cultured bovine adrenal medullary cells. Incubation of cells with orexin-A (100 pM) for 20 min caused a small but significant increase in 14 C -Catecholamine Synthesis from [ 14 C ]tyrosine, but not from l -3,4-dihydroxyphenyl[3- 14 C ]alanine. Orexin-A (100 pM) potentiated the stimulatory effects of acetylcholine (0.3 mM) on 14 C -Catecholamine Synthesis. Orexin-A significantly increased tyrosine hydroxylase activity, which was evident at 1 pM and maximal at 100 pM. 4β-Phorbol-12β-myristate-13α-acetate, an activator of protein kinase C, did not enhance the stimulatory effects of orexin-A on tyrosine hydroxylase activity, while H-7 and staurosporine, inhibitors of protein kinase C, nullified the effects of orexin-A. Orexin-A had little effect on Catecholamine secretion from the cells. Orexin receptor 1 (OX 1 R) but not orexin receptor 2 (OX 2 R) mRNA was detected in bovine adrenal medullary cells by reverse transcriptase-polymerase chain reaction. These findings suggest that orexin-A activates tyrosine hydroxylase and then stimulates Catecholamine Synthesis, probably via activation of the OX 1 R-protein kinase C pathway in adrenal medullary cells.