著者

Liu Yan-Qiu You Song Tashiro Shin-ichi ONODERA Satoshi IKEJIMA Takashi

出版者

The Japanese Pharmacological Society

雑誌

Journal of pharmacological sciences (ISSN:13478613)

巻号頁・発行日

vol.98, no.4, pp.361-371, 2005-08-20

参考文献数

35

被引用文献数

3 26

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Our previous study showed that oridonin isolated from <i>Rabdosia rubescens</i> enhanced phagocytosis of apoptotic cells by macrophage-like U937 cells through tumor necrosis factor (TNF) α and interleukin (IL)-1β release. In this study, we further investigated signaling events involved in oridonin-augmented phagocytosis. Phagocytic stimulation was significantly suppressed by inhibitors, including a phosphoinositide 3-kinases (PI3K) inhibitor (wortmannin), a protein kinase C (PKC) inhibitor (stauroporine), and a phospholipase C (PLC) inhibitor (U73122). Exposure of U937 cells to oridonin caused an increase in PKC activity time- dependently, which was prevented by pretreatment with inhibitors of PI3K and PLC. Simultaneously, the activation of protein kinase B (PKB/Akt) and the increased expression of PLCγ2 were also blocked by wortmannin. In addition, an extracellular signal-regulated kinase (ERK) MAPK inhibitor, PD98059, suppressed oridonin-augmented phagocytosis, whereas the p38 MAPK inhibitor (SB203580) and c-Jun N-terminal kinase (JNK) MAPK inhibitor (SP98059) had no inhibitory effect. Furthermore, pretreatment of U937 cells with anti-TNFα and anti-IL-1β antibodies blocked oridonin-induced phagocytic stimulation as well as phosphorylation of ERK, but did not block the activation of PKC, indicating that these signaling events are triggered by oridonin, whereas secreted TNFα or IL-1β only activate the ERK-dependent pathway. Taken together, oridonin is suggested to enhance phagocytosis of apoptotic bodies by activating PI3K, PKC, and ERK-dependent pathways.<br>

著者

Zhong Qiu Liu Zhi Hong Jiang Kelvin Chan Hua Zhou Yuen Fan Wong Zhao Xiang Bian Hong Xi Xu Liang Liu

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.104, no.3, pp.283, 2007 (Released:2007-07-24)

被引用文献数

1 1

著者

Eun-Joo Shin Jae-Hyung Bach Sung Youl Lee Jeong Min Kim Jinhwa Lee Jau-Shyong Hong Toshitaka Nabeshima Hyoung-Chun Kim

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.116, no.2, pp.137-148, 2011 (Released:2011-06-16)

参考文献数

100

被引用文献数

11 28

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Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.

著者

Takuya Hirata Yoshihiro Keto Toshiyuki Funatsu Shinobu Akuzawa Masao Sasamata

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.104, no.3, pp.263-273, 2007 (Released:2007-07-24)

参考文献数

34

被引用文献数

15 35

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We examined the pharmacological profile of ramosetron, a 5-HT3-receptor antagonist for irritable bowel syndrome with diarrhea, comparing it with those of other 5-HT3-receptor antagonists, alosetron and cilansetron, and the anti-diarrheal agent loperamide. Ramosetron showed high affinity for cloned human and rat 5-HT3 receptors, with Ki values of 0.091 ± 0.014 and 0.22 ± 0.051 nmol/L, respectively, while its affinities for other receptors, transporters, ion channels, and enzymes were negligible. Dissociation of ramosetron from the human 5-HT3 receptor was extremely slow (t1/2 = 560 min), while alosetron (t1/2 = 180 min) and cilansetron (t1/2 = 88 min) dissociated relatively rapidly. Ramosetron competitively inhibited 5-HT-induced contraction of isolated guinea-pig colon, with pA2 values of 8.6 (8.5 – 9.0). Ramosetron given orally also dose-dependently inhibited the von Bezold-Jarisch reflex in rats, with an ED50 value of 1.2 (0.93 – 1.6) μg/kg. In addition, oral ramosetron dose-dependently inhibited restraint stress-induced defecation in rats, with an ED50 value of 0.62 (0.17 – 1.2) μg/kg. In all of these experiments, the potencies of ramosetron were greater than those of alosetron, cilansetron, or loperamide. These results indicate that ramosetron is a highly potent and selective 5-HT3-receptor antagonist, with beneficial effects against stress-induced abnormal defecation in rats.

著者

Gu Kang Pil-Jae Kong Young-Jin Yuh So-Young Lim Sung-Vin Yim Wanjoo Chun Sung-Soo Kim

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.3, pp.325-328, 2004 (Released:2004-03-20)

参考文献数

17

被引用文献数

69 139

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Inflammation is a significant component of chronic neurodegenerative diseases. Cyclooxygenase-2 (COX-2) is expressed in activated microglial cells and appears to be an important source of prostaglandins during inflammatory conditions. To investigate the effect of curcumin on COX-2 gene expression in microglial cells, we treated lipopolysaccharide (LPS)-challenged BV2 microglial cells with various concentrations of curcumin. Curcumin significantly inhibited LPS-mediated induction of COX-2 expression in both mRNA and protein levels in a concentration-dependent manner. COX-2 enzyme activity was also inhibited in accordance with mRNA and protein levels. Furthermore, curcumin markedly inhibited LPS-induced nuclear factor κB (NF-κB) and activator protein 1 (AP-1) DNA bindings. These data suggest that curcumin suppresses LPS-induced COX-2 gene expression by inhibiting NF-κB and AP-1 DNA bindings in BV2 microglial cells.

著者

Hiroshi Ujike Yukitaka Morita

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.96, no.4, pp.376-381, 2004 (Released:2004-12-22)

参考文献数

34

被引用文献数

39 63

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Cannabis consumption may induce psychotic states in normal individuals, worsen psychotic symptoms of schizophrenic patients, and may facilitate precipitation of schizophrenia in vulnerable individuals. Recent studies provide additional biological and genetic evidence for the cannabinoid hypothesis of schizophrenia. Examinations using [3H]CP-55940 or [3H]SR141716A revealed that the density of CB1 receptors, a central type of cannabinoid receptor, is increased in subregions of the prefrontal cortex in schizophrenia. Anandamide, an endogenous cannabinoid, is also increased in the CSF in schizophrenia. A genetic study revealed that the CNR1 gene, which encodes CB1 receptors, is associated with schizophrenia, especially the hebephrenic type. Individuals with a 9-repeat allele of an AAT-repeat polymorphism of the gene may have a 2.3-fold higher susceptibility to schizophrenia. Recent findings consistently indicate that hyperactivity of the central cannabinoid system is involved in the pathogenesis of schizophrenia or the neural mechanisms of negative symptoms.

著者

Tsuneyuki Yamamoto Kusnandar Anggadiredja Takato Hiranita

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.96, no.4, pp.382-388, 2004 (Released:2004-12-22)

参考文献数

51

被引用文献数

16 23

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Growing evidence on the involvement of cannabinoids in the rewarding effects of various kinds of drugs of abuse has suggested that not only the classical dopaminergic and opioidergic, but also the most recently established endocannabinoid system is implicated in the brain reward system. Furthermore, the interplay between the three systems has been shown to be an essential neural substrate underlying many aspects of drug addiction including craving and relapse. Relapse, the resumption of drug taking following a period of drug abstinence, is considered the main hurdle in treating drug addiction. Yet, little is known about its underlying mechanisms. The link between the endocannabinoid system and the arachidonic cascade is currently being clarified. While several findings have, indeed, shown the essential role of the endocannabinoid system in the reinstatement model, the endocannabinoid-arachidonic acid pathway may also be an important part in the neural machinery underlying relapse. This evidence may provide an alternative approach that will open a novel strategy in combating drug addiction.

著者

Atsushi Usami Takuya Sasaki Nobuhiro Satoh Takahiro Akiba Satoshi Yokoshima Tohru Fukuyama Kenzo Yamatsugu Motomu Kanai Masakatsu Shibasaki Norio Matsuki Yuji Ikegaya

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.106, no.4, pp.659-662, 2008 (Released:2008-04-19)

参考文献数

15

被引用文献数

24 33

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Oseltamivir, a widely used anti-influenza drug, inhibits virus neuraminidase. A mammalian homologue of this enzyme is expressed in the brain, yet the effect of oseltamivir on central neurons is largely unknown. Patch-clamp recordings ex vivo revealed that oseltamivir enhanced spike synchronization between hippocampal CA3 pyramidal cells. Time-lapse multineuron calcium imaging revealed that oseltamivir and its active metabolite evoked synchronized population bursts that recruited virtually all neurons in the network. This unique, so-far-unknown, event was attenuated by muscarinic receptor antagonist. Thus, oseltamivir is a useful tool for investigating a new aspect of neural circuit operation.

著者

Taizo Kita George C. Wagner Toshikatsu Nakashima

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.92, no.3, pp.178-195, 2003 (Released:2003-07-23)

参考文献数

161

被引用文献数

95 134 169

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Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson’s disease.

著者

Michio Hashimoto Motoko Maekawa Masanori Katakura Kei Hamazaki Yutaka Matsuoka

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.3, pp.294-300, 2014-03-20 (Released:2014-03-18)

参考文献数

36

被引用文献数

13 47

---

Increasing evidence from the fields of neurophysiology and neuropathology has uncovered the role of polyunsaturated fatty acids (PUFA) in protecting neuronal cells from oxidative damage, controlling inflammation, regulating neurogenesis, and preserving neuronal function. Numerous epidemiological studies have shown that deficits in the dietary PUFA docosahexaenoic acid and eicosapentaenoic acid are associated with the onset and progression of neuropsychiatric illnesses such as dementia, schizophrenia, depression, and posttraumatic stress disorder (PTSD). Recent clinical trials have offered compelling evidence that suggests that n-3 PUFA could reduce depressive, psychotic, and suicidal symptoms, as well as aggression. Although many studies have had the validity of their results questioned because of small sample size, several studies have indicated that n-3 PUFA are useful therapeutic tools for the treatment of dementia, major depression, bipolar disorder, and PTSD. These findings suggest that the pharmacological and nutritional actions of n-3 PUFA may be beneficial in certain neuropsychiatric illnesses. This review article outlines the role of PUFA in neurodevelopment and the regulatory mechanisms in neuronal stem cell differentiation and also the possible use of PUFA as a prescription medicine for the prophylaxis or treatment of neuropsychiatric illnesses such as dementia, mood disorder, and PTSD.

著者

Zhou Wu Hiroshi Nakanishi

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.1, pp.8-13, 2014-09-20 (Released:2014-09-20)

参考文献数

30

被引用文献数

9 62

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Neuroinflammation, inflammation of the brain, is strongly implicated in Alzheimer’s disease (AD), which can be enhanced by systemic inflammation. Therefore, the initiation and progression of AD are affected by systemic diseases such as cardiovascular disease and diabetes. This concept suggests a possible link between periodontitis and AD because periodontitis is a peripheral, chronic infection that elicits a significant systemic inflammatory response. There is now growing clinical evidence that chronic periodontitis is closely linked to the initiation and progression of AD. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to the brain-resident microglia, which in turn initiate neuroinflammation. Furthermore, it is apparent that senescent-type microglia respond in an exaggerated manner to systemic inflammation. It is estimated that a high percentage of adults are suffering from periodontitis, and the prevalence of periodontitis increases with age. Therefore, chronic periodontitis can be a significant source of covert systemic inflammation within the general population. The present review article highlights our current understanding of the link between periodontitis and AD.

著者

Nian-Hong Chen Jian-Wen Liu Jian-Jiang Zhong

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.108, no.2, pp.212-216, 2008 (Released:2008-10-21)

参考文献数

15

被引用文献数

41 79

---

The effect of ganoderic acid Me (GA-Me), which was purified from the fermentation mycelia of the traditional Chinese medicinal mushroom Ganoderma lucidum as reported (Tang W, Gu TY, Zhong JJ. Biochem Eng J. 2006;32:205–210), on anti-invasion was investigated. Wound healing assay indicated that GA-Me inhibited cell migration of 95-D, a human highly metastatic lung tumor cell line, in dose- and time-dependent manners. Results of cell aggregation and adhesion assays showed that GA-Me promoted cell homotypic aggregation and inhibited cell adherence to extracellular matrix (ECM). In addition, GA-Me suppressed matrix metalloproteinases 2/9 (MMP2/9) gene expressions at both mRNA and protein levels in 95-D cells according to qRT-PCR and Western blotting, respectively. The results demonstrated that GA-Me effectively inhibited tumor invasion, and it might act as a new MMP2/9 inhibitor for anti-metastasis treatment of carcinoma cells.

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

---

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.

著者

Ayako Tsuchiya Hisao Nagaya Takeshi Kanno Tomoyuki Nishizaki

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.14182FP, (Released:2014-11-13)

参考文献数

36

被引用文献数

2 16

---

The present study investigated cis-unsaturated free fatty acid (FFA)-regulated glucose uptake. In the cell-free assay of protein tyrosine phosphatase 1B (PTP1B), cis-unsaturated FFAs such as linoleic, linolenic, and oleic acid significantly suppressed PTP1B activity in a concentration (1 – 100 μM)-dependent manner, with the highest potential for oleic acid. Oleic acid (1 μM) stimulated insulin (0.1 nM)-induced phosphorylation of the insulin receptor at Tyr1185 and increased insulin (0.1 nM)-induced phosphorylation of Akt at Thr308 and Ser473 in differentiated 3T3-L1-GLUT4myc adipocytes. In the föerster resonance energy transfer analysis, oleic acid activated Rac1 in PC-12 cells, which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1) inhibitor BX912, or the Akt inhibitor MK2206. Oleic acid (1 μM) significantly increased insulin (0.1 nM)-stimulated glucose uptake in 3T3-L1-GLUT4myc adipocytes, although oleic acid by itself had no effect on the glucose uptake. Taken together, the results of the present study show that oleic acid enhances insulin receptor signaling through a pathway along an insulin receptor/PI3K/PDK1/Akt/Rac1 axis in association with PTP1B inhibition and facilitates insulin-induced glucose uptake into adipocytes.

著者

Ranji Cui Bingjin Li Katsuya Suemaru Hiroaki Araki

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.109, no.4, pp.518-524, 2009 (Released:2009-04-17)

参考文献数

53

被引用文献数

1 6 3

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We have previously reported that sleep patterns are significantly affected by both physical and psychological stress induced by a communication box; however, the mechanism by which stress alters sleep patterns was not established. In the present study, we investigated the role of γ-aminobutyric acid (GABA), acting through the GABAB receptor, on stress-induced changes in sleep patterns. Our results show that physical stress increased the total wakefulness time by increasing sleep latency and inhibiting both rapid eye movement (REM) and non rapid eye movement (NREM) sleep during a 6 h sleep–recording period. The GABAB agonist baclofen (20 pmol/2 μl) attenuated the effects of physical stress on sleep latency, total wakefulness, and NREM sleep, but not total REM sleep. In contrast, psychological stress enhanced total REM sleep and shortened REM sleep latency without altering other sleep patterns. The effect of psychological stress on total REM sleep was also reversed by baclofen. These results suggest that GABA via GABAB receptors may play a role in the regulation of specific sleep patterns by both physical and psychological stress.

著者

Yasukatsu Izumi Katsuyuki Miura Hiroshi Iwao

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.1, pp.1-6, 2014-01-20 (Released:2014-01-18)

参考文献数

30

被引用文献数

9 35

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Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. AVP has important roles in circulatory and water homoeostasis, which are mediated by oxytocin receptors and by AVP receptor subtypes: V1a (mainly vascular), V1b (pituitary), and V2 (renal). Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. Recently, subtype-selective nonpeptide vasopressin-receptor agonists have been developed. A selective V1a-receptor antagonist, relcovaptan, has shown initial positive results in the treatment of Raynaud’s disease, dysmenorrhea, and tocolysis. A selective V1b-receptor antagonist, nelivaptan, has beneficial effects in the treatment of psychiatric disorders. Selective V2-receptor antagonists including mozavaptan, lixivaptan, satavaptan, and tolvaptan induce highly hypotonic diuresis without substantially affecting the excretion of electrolytes. A nonselective V1a/V2-receptor antagonist, conivaptan, is used in the treatment for euvolaemic or hypervolemic hyponatremia. Recent basic and clinical studies have shown that AVP-receptor antagonists, especially V2-receptor antagonists, may have therapeutic potential for heart failure. This review presents current information about AVP and its antagonists.

著者

Tomoko Sakaguchi Hideki Itoh Wei-Guang Ding Keiko Tsuji Iori Nagaoka Yuko Oka Takashi Ashihara Makoto Ito Yoshihiro Yumoto Naoko Zenda Yukei Higashi Youichi Takeyama Hiroshi Matsuura Minoru Horie

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.108, no.4, pp.462-471, 2008 (Released:2008-12-20)

参考文献数

26

被引用文献数

14 30

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QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well as intake of drugs known to affect a cardiac K+ channel encoded by human ether-a-go-go–related gene (HERG). In this paper, we will report a case of drug-induced long QT syndrome associated with an H1-receptor antagonist, hydroxyzine, in which a mutation was identified in the HERG gene. After taking 75 mg of hydroxyzine for several days, a 34-year-old female began to experience repetitive syncope. The deleterious effect of hydroxyzine was suspected because QTc interval shortened from 630 to 464 ms after cessation of the drug. Later on, the patient was found to harbor an A614V-HERG mutation. By using the patch-clamp technique in the heterologous expression system, we examined the functional outcome of the A614V mutation and confirmed a dominant-negative effect on HERG expression. Hydroxyzine concentration-dependently inhibited both wild-type (WT) and WT/A614V-HERG K+ currents. Half-maximum block concentrations of WT and WT/A614V-HERG K+ currents were 0.62 and 0.52 μM, respectively. Thus, accidental combination of genetic mutation and intake of hydroxyzine appeared to have led to a severe phenotype, probably, syncope due to torsade de pointes.

著者

Philippe Lépicier Annie Bibeau-Poirier Caroline Lagneux Marc J. Servant Daniel Lamontagne

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.102, no.2, pp.155-166, 2006 (Released:2006-10-19)

参考文献数

89

被引用文献数

15 24

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The aim of the present article is to review the cardioprotective properties of cannabinoids, with an emphasis on the signaling pathways involved. Cannabinoids have been reported to protect against ischemia in rat isolated hearts, as well as in rats and mice in vivo. Although these effects have been observed mostly with a pre-treatment of a cannabinoid, we report that the selective CB2-receptor agonist JWH133 is able to reduce infarct size when administered either before ischemia, during the entire ischemic period, or just upon reperfusion. Little is known about the signaling pathways involved in these cardioprotective effects. Likely candidates include protein kinase C (PKC) and mitogen-activated protein kinases (MAPK) since they are activated during ischemia-reperfusion and contribute to the protective effect ischemic preconditioning. The use of pharmacological inhibitors suggests that PKC, p38 MAPK, and p42/p44 MAPK (ERK1/2) contribute to the protective effect of cannabinoids. In addition, perfusion with JWH133 in healthy hearts caused an increase in both p38 MAPK phosphorylation level and activity, whereas the CB1-receptor agonist ACEA was associated with an increase in the phosphorylation status of both ERK1 and ERK2 without any change in activity. During ischemia, both agonists doubled p38 MAPK activity, whereas ERK1/2 phosphorylation level and activity during reperfusion were enhanced only by the CB1-receptor agonist. Finally, although nitric oxide (NO) was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an apparently controversial effect on myocardial survival, our data suggest that NO may contribute to the cardioprotective effect of some cannabinoids.

著者

Kim Ki Jung Cho Hyeong Seok Choi Se Joon Jeun Seung Hyun Kim Seong Yun Sung Ki-Wug

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.107, no.1, pp.57-65, 2008

被引用文献数

5

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The pharmacological action of riluzole, a drug that has been approved as a neuroprotective agent for the treatment of amyotrophic lateral sclerosis, has not yet been established. We examined the effects of riluzole on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells using the whole-cell voltage clamp technique combined with a fast drug application method. Co-application of riluzole (1 – 300 μM, 5 s) produced a dose-dependent reduction in peak amplitudes and in the rise slope of the currents induced by 2 μM 5-HT. In addition, 5-HT₃–mediated currents evoked by dopamine, a partial 5-HT₃–receptor agonist, were inhibited by riluzole co-application. These inhibitory effects were clearly shown at low concentrations of 5-HT. The decay time constants of the receptor desensitization and deactivation were also significantly attenuated by riluzole. G-protein inhibitors (pertussis toxin and guanosine 5'-[β-thio] diphosphate) did not completely block these inhibitory actions of riluzole. These results indicate that riluzole inhibits 5-HT₃–induced ion currents directly by slowing channel activation in NCB-20 neuroblastoma cells.<br>

著者

Ken-Ichi Furukawa

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.129-137, 2014-02-20 (Released:2014-02-19)

参考文献数

84

被引用文献数

1 12

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Aortic valve calcification can aggravate aortic stenoses, and it is a significant cause of sudden cardiac death. The increasing number of patients with age-related calcification is a problem in developed nations. However, the only treatment option currently available is highly invasive cardiac valve replacement. Therefore, clarification of the etiology of calcification is urgently needed to develop drug therapies and prevention methods. Recent studies have revealed that calcification is not a simple sedimentation of a mineral through a physicochemical phenomenon; various factors dynamically contribute to the mechanism. Further, we are finally beginning to understand the cellular origins of calcification, which had been unclear for a long time. Based on these findings that help to clarify potential drug targets, we expect to establish drug therapies that reduce the stress on patients. In this paper, I introduce the latest findings on cells that are most likely to contribute to calcification and on calcification-related factors that may lead to the development of drug therapies.