著者

Makoto Bannai Nobuhiro Kawai

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.118, no.2, pp.145-148, 2012 (Released:2012-02-16)

参考文献数

28

被引用文献数

5 36

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Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine’s effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.

著者

Ryosuke Tanaka Junji Takayama Masanori Takaoka Yohko Sugino Mamoru Ohkita Yasuo Matsumura

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

vol.126, no.3, pp.291-291, 2014 (Released:2014-11-20)

著者

Yoshihiro Uesawa Shigeru Hishinuma Masaru Shoji

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

vol.124, no.2, pp.160-168, 2014-02-20 (Released:2014-02-19)

参考文献数

28

被引用文献数

3 6

---

There is argument whether non-sedative properties of histamine H1–receptor antagonists (antihistamines) are determined by their active extrusions from the brain via P-glycoprotein or their restricted penetration through the blood-brain barrier. We have reported that sedative and non-sedative antihistamines can be well discriminated by measuring changes in their binding to H1 receptors upon receptor internalization in intact cells, which depends on their membrane-penetrating ability. In this study, molecular determinants responsible for sedative and non-sedative properties of antihistamines were evaluated by quantitative structure-activity relationship (QSAR) analyses. Multiple regression analyses were applied to construct a QSAR model, taking internalization-mediated changes in the binding of antihistamines as objective variables and their structural descriptors as explanatory variables. The multiple regression model was successfully constructed with two explanatory variables, i.e., lipophilicity of the compounds at physiological pH (logD) and mean information content on the distance degree equality (IDDE) (r2 = 0.753). The constructed model discriminated between sedative and non-sedative antihistamines with 94% accuracy for external validation. These results suggest that logD and IDDE concerning lipophilicity and molecular shapes of compounds, respectively, predominantly determine the membrane-penetrating ability of antihistamines for their side effects on the central nervous system.

著者

Zhi-Bin Lin

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.99, no.2, pp.144-153, 2005 (Released:2005-10-18)

参考文献数

51

被引用文献数

79 118 141

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Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi or Reishi) has been used for a long time in China to prevent and treat various human diseases. G. lucidum polysaccharides extracted from G. lucidum are one of efficacious ingredient groups of G. lucidum. A number of reports have demonstrated that G. lucidum polysaccharides modulate immune function both in vivo and in vitro. The immuno-modulating effects of G. lucidum polysaccharides were extensive, including promoting the function of antigen-presenting cells, mononuclear phygocyte system, humoral immunity, and cellular immunity. Cellular and molecular mechanisms, possible receptors involved, and triggered signaling cascades have also been studied in vitro. However, whole animal experiments are still needed to further establish the mechanism of the immuno-modulating effects by G. lucidum. Evidence-based clinical trials are also needed.

著者

Takeo Kubota Kunio Miyake Takae Hirasawa Kaoru Nagai Tsuyoshi Koide

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

vol.113, no.1, pp.3-8, 2010 (Released:2010-05-17)

参考文献数

66

被引用文献数

6 8

---

Epigenetics is a mechanism that regulates gene expression not depending on the underlying DNA sequence, but on the chemical modifications of DNA and histone proteins. Defects in the factors involved in epigenetic regulation cause congenital neurodevelopmental diseases, and thus, epigenetic regulation is essential for normal brain development. Besides these intrinsic defects, it is becoming increasingly apparent that extrinsic factors, such as insufficient nutrition, psychiatric drugs, and mental stress, also alter epigenetic regulation. Therefore, environmental factors may lead to “acquired” neurodevelopmental disorders through the failure of epigenetic regulation. Epigenetics is a biological key to understand the gene–environment interactions in neurodevelopmental disorders. As the mechanism is reversible, its comprehensive understanding will result in the development of new therapies for these disorders.

著者

Hideaki Noguchi Kazuhiro Kitazumi Megumi Mori Toshiharu Shiba

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.94, no.3, pp.246-251, 2004 (Released:2004-03-20)

参考文献数

22

被引用文献数

17 21

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The encephalographic (EEG) properties of zaleplon were investigated in comparison with those of other sedative hypnotics in conscious rats with chronically implanted electrodes. The oral administration of zaleplon (0.25 – 1.0 mg/kg), triazolam (0.0625 – 0.25 mg/kg), zopiclone (1.0 – 4.0 mg/kg), brotizolam (0.0625 – 0.25 mg/kg), and nitrazepam (0.125 – 0.5 mg/kg) lengthened the total sleep in a dose-dependent manner. On distribution of sleep-wakefulness stages, zaleplon, in particular, increased the slow wave deep sleep (SWDS), whereas triazolam, brotizolam, and nitrazepam increased the slow wave light sleep (SWLS) in a dose-dependent manner. Zopiclone significantly increased the SWDS at a dose of 2 mg/kg and both the SWLS and the SWDS at a dose of 4 mg/kg. All tested hypnotics caused no influence on fast wave sleep (FWS) at doses tested. The appearance of the sleep-inducing activity of zaleplon was more rapid than those of any compounds tested, and zaleplon significantly increased the relative EEG power density in the delta frequency band over that of triazolam at 20 and 30 min after the administration in the spectral analysis. Therefore, the present findings suggest that the non-benzodiazepine zaleplon can be expected to exhibit high practical potential as a hypnotic and is characterized by an increase in SWDS with rapid onset of hypnotic action.

著者

Kenji Iizuka Takuji Machida Masahiko Hirafuji

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.125, no.2, pp.125-131, 2014-06-20 (Released:2014-06-19)

参考文献数

49

被引用文献数

28 132

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Skeletal muscle plays a key role in postural retention as well as locomotion for maintaining the physical activities of human life. Skeletal muscle has a second role as an elaborate energy production and consumption system that influences the whole body’s energy metabolism. Skeletal muscle is a specific organ that engenders a physical force, and exercise training has been known to bring about multiple benefits for human health maintenance and/or improvement. The mechanisms underlying the improvement of the human physical condition have been revealed: skeletal muscle synthesizes and secretes multiple factors, and these muscle-derived factors, so-called as myokines, exert beneficial effects on peripheral and remote organs. In this short review, we focus on the third aspect of skeletal muscle function — namely, the release of multiple types of myokines, which constitute a broad network for regulating the function of remote organs as well as skeletal muscle itself. We conclusively show that skeletal muscle is one of the endocrine organs and that understanding the mechanisms of production and secretion of myokines may lead to a new pharmacological approach for treatment of clinical disorders.

著者

William K.K. Wu Chi Hin Cho

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

vol.94, no.4, pp.348-358, 2004 (Released:2004-04-20)

参考文献数

105

被引用文献数

22 45

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Increasing use of tobacco and its related health problems are a great concern in the world. Recent epidemiological findings have demonstrated the positive association between cigarette smoking and several gastrointestinal (GI) diseases, including peptic ulcer and cancers. Interestingly, smoking also modifies the disease course of ulcerative colitis (UC). Nicotine, a major component of cigarette smoke, seems to mediate some of the actions of cigarette smoking on the pathogenesis of GI disorders. Nicotine worsens the detrimental effects of aggressive factors and attenuates the protective actions of defensive factors in the processes of development and repair of gastric ulceration. Nicotine also takes part in the initiation and promotion of carcinogenesis in the GI tract. In this regard, nicotine and its metabolites are found to be mutagenic and have the ability to modulate cell proliferation, apoptosis, and angiogenesis during tumoriogenesis through specific receptors and signalling pathways. However, to elucidate this complex pathogenic mechanism, further study at the molecular level is warranted. In contrast, findings of clinical trials give promising results on the use of nicotine as an adjuvant therapy for UC. The beneficial effect of nicotine on UC seems to be mediated through multiple mechanisms. More clinical studies are needed to establish the therapeutic value of nicotine in this disease.

著者

Shrabanti Dev Hiroyuki Mizuguchi Asish K. Das Chiyo Matsushita Kazutaka Maeyama Hayato Umehara Takayuki Ohtoshi Jun Kojima Kiyotaka Nishida Kunihiko Takahashi Hiroyuki Fukui

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.107, no.2, pp.159-166, 2008 (Released:2008-06-20)

参考文献数

35

被引用文献数

26 29

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It has been shown that probiotic bacteria are effective for the treatment of allergic diseases. As histamine plays a central role in allergic diseases, it is possible that probiotic bacteria affect the allergy-related histamine signaling. Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. In the nasal allergy model rats made by sensitization and provocation with toluene 2,4-diisocyanate (TDI) for 3 weeks, TDI provocation caused acute allergy–like behaviors along with significant up-regulation of histamine H1 receptor (H1R) and histidine decarboxylase (HDC) mRNA expression, increased HDC activity, histamine content, and [3H]mepyramine binding activity in nasal mucosa. Prolonged treatment with Lac-B (40 mg/rat, p.o.) significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling. Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. Suppression of histamine signaling may be a novel target of probiotics in preventing allergic diseases.

著者

Yu Tahara Shigenobu Shibata

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.3, pp.320-335, 2014-03-20 (Released:2014-03-18)

参考文献数

184

被引用文献数

31 56

---

The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep–wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light–dark cycle, food intake, and drug administration. In this review, we focus on the central and peripheral circadian clock systems in response to drugs, food, and nutrition. We also discuss the adaptation and anticipation mechanisms of our body with regard to clock system regulation of various kinetic and dynamic pathways, including absorption, distribution, metabolism, and excretion of drugs and nutrients. “Chrono-pharmacology” and “chrono-nutrition” are likely to become important research fields in chrono-biological studies.

著者

Akihiro Tanaka Katsuya Suemaru Hiroaki Araki

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.105, no.1, pp.1-5, 2007 (Released:2007-09-20)

参考文献数

27

被引用文献数

34 35

---

In clinical practice, the measurement of endogenous serum substances in order to estimate glomerular filtration rate (GFR) is commonly performed, and the serum creatinine level has become the most commonly used serum marker of renal function. However, the measurement of the serum creatinine concentration can sometimes lead to an overestimation of GFR, especially in the elderly. In recent years, it has been suggested that GFR can be predicted based on the serum cystatin C concentrations and that the serum cystatin C concentration is not influenced by gender or age. A recent meta-analysis demonstrated that serum cystatin C is a better marker for GFR than serum creatinine. In clinical practice, it has been suggested that serum cystatin C can optimize early detection for diabetic or hypertensive nephropathy. In addition, the use of serum cystatin C is possibly more appropriate for establishing an appropriate dose adjustment of drugs that are mainly eliminated by the kidney.

著者

Hiroyuki Nakamura Toshihiko Murayama

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.3, pp.307-312, 2014-03-20 (Released:2014-03-18)

参考文献数

30

被引用文献数

27 37

---

The arachidonic acid (AA) cascade is regulated mainly by the actions of two rate-limiting enzymes, phospholipase A2 (PLA2) and inducible cyclooxygenase-2 (COX-2). PLA2 acts to generate AA, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to prostaglandin production. Amongst more than 30 members of the PLA2 family, cytosolic PLA2α (cPLA2α, group IVA) plays a major role in releasing AA from cellular membranes. Sphingolipids are a novel class of bioactive lipids that play key roles in the regulation of several cellular processes including growth, differentiation, inflammatory responses, and apoptosis. Recent studies implicated a regulatory function of sphingolipids in prostaglandin production. Whereas ceramide-1-phosphate and lactosylceramide activate cPLA2α directly, sphingosine-1-phosphate induces COX-2 expression. Sphingomyelin has been shown to inhibit the activity of cPLA2α. In addition, several sphingolipid analogs including a therapeutic agent currently used clinically are also reported to be inhibitors of cPLA2α. This review explores the role of sphingolipids in the regulation of cPLA2α and COX-2.

著者

Yu Ohmura Emily M. Jutkiewicz Mitsuhiro Yoshioka Edward F. Domino

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

vol.117, no.2, pp.121-124, 2011 (Released:2011-10-17)

参考文献数

15

被引用文献数

6 15

---

Abrupt nicotine cessation after chronic use disrupts monoaminergic systems and causes withdrawal signs/symptoms. In this study, the precursor of serotonin 5-hydroxytryptophan (5-HTP) relieved nicotine withdrawal signs. (−)-Nicotine bitartrate or equimolar sodium tartrate was infused into each rat via a s.c. osmotic minipump for 7 days. Somatic abstinence signs (teeth-chattering/chews and shakes, etc.) were counted one day after pump removal. Somatic signs were attenuated by the i.p. injection of 5-HTP, but not by NSD-1015, a centrally-acting L-aromatic amino acid decarboxylase inhibitor, indicating that 5-HTP mitigates somatic signs mainly through its conversion to 5-HT.

著者

Eri Tsukagoshi Mitsuru Kawaguchi Takashi Shinomiya Masanobu Yoshikawa Toshihiko Kawano Migiwa Okubo Kohei Sawaki

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

vol.115, no.2, pp.221-229, 2011 (Released:2011-02-18)

参考文献数

32

被引用文献数

3 8 4

---

Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, we investigated the effect of repetitive administration of diazepam (DZP) on salivary secretion and expression of DBI mRNA and peptide. Moreover, mRNA expression of PBR and pituitary adenylate cyclase–activating polypeptide (PACAP), a transcriptional regulator for DBI promoter, was evaluated after repetitive administration of DZP. Repetitive administration, but not single administration, of 0.4 mg/kg DZP caused inhibition of salivary secretion and enhanced expression of DBI, PACAP, and PBR mRNA in rat salivary gland, with an increase in production of DBI peptide. These results suggest that repetitive administration of DZP stimulates DBI production, which may result in an increase in the suppressive effect of DZP on salivary secretion.

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

Golmaryam Sarlak Anorut Jenwitheesuk Banthit Chetsawang Piyarat Govitrapong

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

vol.123, no.1, pp.9-24, 2013-09-20 (Released:2013-09-20)

参考文献数

231

被引用文献数

23 62

---

Neural aging as a progressive loss of function involves central and peripheral post-mitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The self-renewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cell-cycle– and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

著者

Masaki Michishita Tatsuya Uto Ryota Nakazawa Hisashi Yoshimura Kikumi Ogihara Yuko Naya Tsuyoshi Tajima Daigo Azakami Seigo Kishikawa Toshiro Arai Kimimasa Takahashi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.121, no.4, pp.339-342, 2013-04-20 (Released:2013-04-19)

参考文献数

15

被引用文献数

8 15

---

Canine hemangiopericytoma (CHP) is characterized by frequent local recurrence and increased invasiveness. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in tumors. The aim of the present study was to investigate the effect of a single dose of bevacizumab on a xenograft model of CHP. VEGF protein was secreted from cultured CHP cells and interacted with bevacizumab. Bevacizumab treatment suppressed tumor growth by inhibiting tumor angiogenesis, whereas no significant differences were observed in the proliferation index and apoptosis rates of treated and untreated mice. Thus, bevacizumab had antitumor effects in a xenograft model of CHP.

著者

Tomohisa Mori Kazumi Yoshizawa Masahiro Shibasaki Tsutomu Suzuki

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.120, no.2, pp.70-76, 2012 (Released:2012-10-19)

参考文献数

37

被引用文献数

5 8

---

The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers are trying to elucidate the mechanisms that underlie the discriminative stimulus effects of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, the patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and ketamine, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. However, the mechanisms of the discriminative stimulus effects of hallucinogenic drugs are not yet fully clear. This review will briefly focus on the recent findings regarding hallucinogenic/psychotomimetic drug–induced discriminative stimulus effects in animals. In summary, recent research has demonstrated that there are at least two plausible mechanisms that can explain the cue of the discriminative stimulus effects of hallucinogenic drugs; one is mediated mainly by 5-HT2 receptors, and the other is mediated through sigma-1 (σ1)-receptor chaperone regulated by endogenous hallucinogenic ligand.

著者

Nobuaki Egashira Ai Nogami Katsunori Iwasaki Ayumi Ishibashi Naoki Uchida Kotaro Takasaki Kenichi Mishima Ryoji Nishimura Ryozo Oishi Michihiro Fujiwara

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.116, no.3, pp.316-320, 2011 (Released:2011-07-15)

参考文献数

15

被引用文献数

32 33

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In the present study, we investigated the effect of the Kampo medicine Yokukansan (YKS) on pentobarbital-induced sleep in group-housed and socially isolated mice. Socially isolated mice showed shorter sleeping time than the group-housed mice. YKS (300 mg/kg, p.o.) prolonged the pentobarbital-induced sleeping time in socially isolated mice without affecting pentobarbital sleep in group-housed mice. The prolongation of sleeping time by YKS was reversed by bicuculline (3 mg/kg, i.p.) and flumazenil (3 mg/kg, i.p.), but not WAY100635. These findings suggest that the GABAA – benzodiazepine receptor complex, but not 5-HT1A receptors, is involved in the reversal effect of YKS on the decrease of pentobarbital sleep by social isolation.

著者

Hiroko Sonoda Worapat Prachasilchai Hiroaki Kondo Naoko Yokota-Ikeda Sayaka Oshikawa Katsuaki Ito Masahiro Ikeda

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.112, no.2, pp.242-246, 2010 (Released:2010-02-18)

参考文献数

15

被引用文献数

9 11

---

Overexpression of heat shock protein 70 kDa (HSP70) is known to confer cellular protection against ischemia–reperfusion (I/R) injury. Radicicol, a HSP90 inhibitor, has been reported to induce the expression of HSP70 protein. Here we studied whether radicicol attenuated renal I/R injury in vivo. Treatment of mice with radicicol ameliorated renal I/R injury and increased renal HSP70 mRNA and protein. Administration of radicicol with quercetin, an inhibitor of HSP70 induction, eliminated the renoprotective effect of radicicol. Our results suggest that the up-regulation of renal HSP70 protein by radicicol leads to a novel drug therapy against renal I/R injury.