著者

Takashi Ebisawa

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.103, no.2, pp.150-154, 2007 (Released:2007-02-20)

参考文献数

31

被引用文献数

59 77

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Genetic analyses of circadian rhythm sleep disorders (CRSD), such as familial advanced sleep phase syndrome (ASPS) and delayed sleep phase syndrome (DSPS), and morningness-eveningness revealed the relationship between variations in clock genes and diurnal change in human behaviors. Variations such as T3111C in the Clock gene are reportedly associated with morningness-eveningness. Two of the pedigrees of familial ASPS (FASPS) are caused by mutations in clock genes: the S662G mutation in the Per2 gene or the T44A mutation in the casein kinase 1 delta (CK1δ) gene, although these mutations are not found in other pedigrees of FASPS. As for DSPS, a missense variation in the Per3 gene is identified as a risk factor, while the one in the CK1ε gene is thought to be protective. These findings suggest that further, as yet unidentified, gene variations are involved in human circadian activity. Many of the CRSD-relevant variations reported to date seem to affect the phosphorylation status of the clock proteins. A recent study using mathematical models of circadian rhythm generation has provided a new insight into the role of phosphorylation in the molecular mechanisms of these disorders.

著者

Eiichi Hinoi Yukio Yoneda

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.1106090573, (Released:2011-06-10)

参考文献数

67

被引用文献数

12 21

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The prevailing view is that L-glutamate (Glu) functions as an excitatory amino acid neurotransmitter through a number of molecular machineries required for the neurocrine signaling at synapses in the brain. These include Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Although relatively little attention has been paid to the functional expression of these molecules required for glutamatergic signaling in peripheral tissues, recent molecular biological analyses including ours give rise to a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system in several peripheral and non-neuronal tissues, including bone and cartilage. In particular, a drastic increase is demonstrated in the endogenous levels of both Glu and aspartate in the synovial fluid with intimate relevance to increased edema and sensitization to thermal hyperalgesia in experimental arthritis models. However, to date, there is only limited information about the physiological and pathological significance of glutamatergic signaling machineries expressed by articular synovial tissues. In this review, we have outlined the role of Glu in synovial fibroblasts in addition to the possible involvement of glutamatergic signaling machineries in the pathogenesis of joint diseases such as rheumatoid arthritis.

著者

Eun-Joo Shin Phil Ho Lee Hyun Ji Kim Toshitaka Nabeshima Hyoung-Chun Kim

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.106, no.1, pp.22-27, 2008 (Released:2008-01-22)

参考文献数

42

被引用文献数

15 16

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Drug abuse involving dextromethorphan, an antitussive, has been a social problem in various geographic locations since the 1960s. Ironically, high doses of the drug confer neuroprotective activity with central nervous system and behavioral effects. Accumulating evidence suggests that metabolism to phencyclidine-like dextrorphan is not essential for the neuroprotective activity of dextromethorphan. Here, we review the neuroprotective properties of dextromethorphan and its potential for abuse and the potential neuroprotective effects of the drug’s analogs and 3-hydroxymorphinan, a metabolite of dextromethorphan. These compounds may provide a novel therapeutic direction for the treatment of neurodegenerative diseases such as convulsive or parkinsonian-like disorders.

著者

Parle Milind Dhingra Dinesh

出版者

The Japanese Pharmacological Society

雑誌

Journal of pharmacological sciences (ISSN:13478613)

巻号頁・発行日

vol.93, no.2, pp.129-135, 2003-10-01

被引用文献数

6 79

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Alzheimer's disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory. The occurrence of Alzheimer's disease is commonplace among the Asian population, particularly among senior citizens. The present study was undertaken to assess the potential of ascorbic acid as a memory-enhancer. Swiss mice of either sex were employed in the present investigation. Elevated plus-maze and passive-avoidance apparatus served as the exteroceptive behavioral models, and diazepam-, scopolamine-, and aging-induced amnesia served as the interoceptive behavioral models. Ascorbic acid (60, 120 mg/kg) injected for 3 and 8 consecutive days improved learning and memory of aged mice as indicated by decreased transfer-latency and increased step-down latency. Furthermore, ascorbic acid provided protection to the young animals from scopolamine- and diazepam-induced impairment of memory. Ascorbic acid was found to be more potent than piracetam as reflected by the smaller dose, more pronounced effect, and quicker onset of action. Ascorbic acid has shown promise as a powerful memory-improving agent particularly effective in aged animals. Hence, ascorbic acid might prove to be a useful memory-restorative agent in the treatment of dementia seen in elderly individuals. The underlying mechanism of action of ascorbic acid may be attributed to its antioxidant property.<br>

著者

Kenji Kawakita Hisashi Shinbara Kenji Imai Fumihiko Fukuda Tadashi Yano Kinya Kuriyama

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.100, no.5, pp.443-459, 2006 (Released:2006-06-24)

参考文献数

98

被引用文献数

78 98

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The mechanisms of action of acupuncture and moxibustion as reported by Japanese researchers are reviewed. The endogenous opioid-mediated mechanisms of electroacupuncture (EA) as used in China are well understood, but these are only one component of all mechanisms of acupuncture. These studies emphasize the similarity of the analgesic action of EA to various sensory inputs to the pain inhibition mechanisms. In Japanese acupuncture therapy, careful detection of the acupuncture points and fine needling technique with comfortable subjective sensation are considered important. The role of polymodal receptors (PMR) has been stressed based on the facts that PMRs are responsive to both acupuncture and moxibustion stimuli, thermal sensitivity is essential in moxibustion therapy, and the characteristics of acupuncture points and trigger points are similar to those of sensitized PMRs. Acupuncture and moxibustion are also known to affect neurons in the brain reward systems and blood flow in skin, muscle, and nerve. Axon reflexes mediated by PMRs might be a possible mechanism for the immediate action of acupuncture and moxibustion. Reports on the curative effects of acupuncture on various digestive and urological disorders are also reviewed briefly.

著者

HARAUCHI Toshio TAKANO Kyoji MATSUURA Minoru YOSHIZAKI Toshio

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.40, no.4, pp.491-499, 1986

被引用文献数

4 24

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Descarboxyprothrombin (PIVKA II) is a precursor of prothrombin without biological activity, and it increases with vitamin K deficiency. We studied the time course changes in liver and plasma levels of PIVKA II during the progress of vitamin K deficiency in rats. Good correlation was observed between liver PIVKA II and plasma PIVKA II and between liver or plasma PIVKA II and plasma prothrombin in experiments in which rats were fed a vitamin K-deficient diet. Feeding of a vitamin K-deficient diet or fasting caused marked increases in liver and plasma PIVKA II in male rats and a weaker response in female rats. Warfarin, a vitamin K antagonist, caused an abrupt increase in liver PIVKA II, but the increase in plasma PIVKA II was delayed about 3 hr. Plasma prothrombin decreased from about 30 min later. Factor VII decreased similarly to prothrombin, and changes in the prothrombin time and activated partial thromboplastin time were slower than the changes in these substances. Sex differences were not seen in these warfarin actions. These observations indicate that liver and plasma PIVKA II are sensitive markers of vitamin K deficiency in rats, and assay of PIVKA II can be useful for analyzing the action mechanism of drugs which influence blood coagulation.