著者

Miki Nonaka Nagomi Kurebayashi Takashi Murayama Masami Sugihara Kiyoshi Terawaki Seiji Shiraishi Kanako Miyano Hiroshi Hosoda Shosei Kishida Kenji Kangawa Takashi Sakurai Yasuhito Uezono

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.Suppl., pp.S35-S39, 2017 (Released:2017-06-24)

参考文献数

14

被引用文献数

2 9

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Cancer was considered an incurable disease for many years; however, with the development of anticancer drugs and state-of-the art technologies, it has become curable. Cardiovascular diseases in patients with cancer or induced by cancer chemotherapy have recently become a great concern. Certain anticancer drugs and molecular targeted therapies cause cardiotoxicity, which limit the widespread implementation of cancer treatment and decrease the quality of life in cancer patients significantly. The anthracycline doxorubicin (DOX) causes cardiotoxicity. The cellular mechanism underlying DOX-induced cardiotoxicity include free-radical damage to cardiac myocytes, leading to mitochondrial injury and subsequent death of myocytes. Recently, circulating orexigenic hormones, ghrelin and des-acyl ghrelin, have been reported to inhibit DOX-induced cardiotoxicity. However, little is known about the molecular mechanisms underlying their preventive effects. In the present study, we show the possible mechanisms underlying the effects of ghrelin and des-acyl ghrelin against DOX-induced cardiotoxicity through in vitro and in vivo researches.

著者

Keita Mizuno Toru Kono Yasuyuki Suzuki Chika Miyagi Yuji Omiya Kanako Miyano Yoshio Kase Yasuhito Uezono

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.13244FP, (Released:2014-04-29)

参考文献数

40

被引用文献数

9 43

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The acute peripheral neuropathy induced by oxaliplatin treatment occurs very frequently and is aggravated by exposure to cold. Goshajinkigan (GJG), a traditional Japanese (kampo) medicine, was recently shown to be effective against oxaliplatin-induced acute neuropathy. However, because the effects of GJG and its mechanism in relation to those of its ingredients and its mechanism are not well understood, we examined the effects of GJG on acute neuropathy. Further, we investigated whether GJG affects the functions and gene expressions of transient receptor potential (TRP) channels using a rat model of oxaliplatin-induced neuropathy. Administration of oxaliplatin increased withdrawal responses from cold stimulation, and GJG or calcium gluconate/magnesium sulfate significantly inhibited the oxaliplatin-induced cold hypersensitivity. Application of menthol, a TRPA1/TRPM8 agonist, or allyl isothiocyanate (AITC), a selective TRPA1 agonist, to the hind paw of oxaliplatin-treated rats enhanced the nocifensive behaviors evoked by each agonist, whereas oxaliplatin had no significant effect on nocifensive behaviors evoked by capsaicin, a TRPV1 agonist. GJG treatment reduced menthol- or AITC-evoked withdrawal responses potentiated by oxaliplatin. Furthermore, GJG suppressed the increase of TRPA1 and TRPM8 mRNA expression induced by oxaliplatin in dorsal root ganglia. These findings suggest that GJG prevented oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels, especially TRPA1 and TRPM8.

著者

Kanako Miyano Yuka Sudo Akinobu Yokoyama Kazue Hisaoka-Nakashima Norimitsu Morioka Minoru Takebayashi Yoshihiro Nakata Yoshikazu Higami Yasuhito Uezono

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.14R13CP, (Released:2014-11-22)

参考文献数

30

被引用文献数

7 45

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The G protein–coupled receptors (GPCRs) form the largest and the most versatile superfamily that share a seven-transmembrane-spanning architecture. GPCR-signaling is involved in vision, taste, olfaction, sympathetic/parasympathetic nervous functions, metabolism, and immune regulation, indicating that GPCRs are extremely important therapeutic targets for various diseases. Cellular dielectric spectroscopy (CDS) is a novel technology that employs a label-free, real-time and cell-based assay approach for the comprehensive pharmacological evaluation of cells that exogenously or endogenously express GPCRs. Among the biosensors that use CDS technology, the CellKeyTM system not only detects the activation of GPCRs but also distinguishes between signals through different subtypes of the Gα protein (Gs, Gi/o, and Gq). In this review, we discuss the traditional assays and then introduce the principles by which the CellKeyTM system evaluates GPCR activation, followed by a perspective on the advantages and future prospects of this system.