Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Volume 91 , Issue 2
Showing 1-12 articles out of 12 articles from the selected issue
Critical Review
  • Ryo Saito, Yukio Takano, Hiro-o Kamiya
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 87-94
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The emetic response is primarily a protective reflex occurring in a wide variety of vertebrates in response to the ingestion of toxic compounds. The role of the nuclei in the brainstem, including the area postrema, nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the central pattern generator for vomiting, as well as the involvement of the abdominal visceral innervation relevant to the emetic reflex, have all been discussed by many researchers. The introduction of serotonin 5-HT3-receptor antagonists into clinical practice allowed for a dramatic improvement in the management of vomiting. However, vomiting still remains a significant problem. The mechanism of the emetic response is even more complicated than was first thought. This review attempts to bring together some of the evidence suggesting the roles of substance P and its receptor, neurokinin NK1 receptor, in the brainstem nuclei in the development of emesis. Accordingly, NK1-receptor antagonists might represent novel drugs for the management of major types of emesis.
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Full Papers
  • Mi-Hyeon Jang, Min-Chul Shin, Sabina Lim, Seung-Moo Han, Hi-Joon Park, ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 95-104
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    To investigate whether bee venom (BV) induces apoptosis, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling assay, 4,6-diamidino-2-phenylindole staining, flow cytometric analysis, and DNA fragmentation assay were performed on NCI-H1299 lung cancer cells treated with BV. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with BV exhibit several features of apoptosis. In addition, reverse transcription-polymerase chain reaction and prostaglandin E2 (PGE2) immunoassay were performed to verify whether BV possesses an inhibitory effect on the expression of cyclooxygenase (COX) and PGE2 synthesis. Expression of COX-2 mRNA and synthesis of PGE2 were inhibited by BV. These results suggest the possibility that BV may exert an anti-tumor effect on human lung cancer.
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  • Yoshihito Funaki, Motohisa Kato, Ren Iwata, Eiko Sakurai, Eiichi Sakur ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 105-112
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [11C]donepezil. [5-11C-methoxy]Donepezil was synthesized by O-methylation using [11C]methyl triflate. The binding of [11C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [11C]donepezil to AChE in the rat brain. The IC50 value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the Bmax and Kd of [11C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [11C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-11C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography.
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  • Kageyoshi Ono, Akira Saito, Katsutoshi Goto, Yutaka Kasuya, Koki Shige ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 113-124
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The physiological role of endogenous neuropeptide Y (NPY) in sympathetic neurotransmission was examined in rat and guinea pig vas deferens (VD), using α-chymotrypsin (α-CT). NPY-like immunoreactivity was detected in the longitudinal muscle layer of VD densely in rats but sparsely in guinea pigs, and it disappeared following surgical denervation. Under blockade of the prejunctional α2-adrenergic autoinhibition, α-CT potentiated the phasic contraction in rat, but not guinea pig, VD induced by trains of transmural nerve stimulation (TNS) in a frequency-dependent manner, which was reproducible during repeated applications and not affected by pretreatment with capsaicin. In contrast, α-CT did not potentiate the twitch response or contractions induced respectively by a single pulse TNS or by direct electrical stimulation to the smooth muscle. Exogenously applied NPY suppressed the twitch response, which was cancelled by α-CT, and excitatory junction potentials, although it affected neither spontaneous junction potentials nor the direct electrical stimulation-induced contraction. These observations provided further evidence to support that NPY is released endogenously by TNS at high frequency, acting prejunctionally to suppress sympathetic neurotransmission. Thus, the protease α-CT proved itself to be a useful tool to reveal a functional role of endogenously released peptides.
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  • Toyoshi Umezu, Masatoshi Morita
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 125-135
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The present study examines the mechanism that underlies the ability of menthol (ME), a major constituent of peppermint oil, to promote mouse ambulation. We initially confirmed that bupropion (BUP), a dopamine (DA) uptake inhibitor, promotes ambulation in ICR mice. Since the subcutaneous administration of ME produced similar effects in mice, we investigated the effects of ME on ambulation when combined with BUP. The results showed that BUP potentiated the effect of ME on mouse ambulation. We then examined effects of the DA antagonists chlorpromazine, haloperidol, fluphenazine, spiperone, and SCH12679 on the ability of BUP and ME to promote ambulation. All of these DA antagonists attenuated the effects of BUP and ME. Prior exposure to reserpine, which depletes monoamines, caused decreased sensitivity to the ability of BUP and of ME in promoting ambulation. The tyrosine hydroxylase inhibitor α-methyl-p-tyrosine, similarly decreased subsequent sensitivity to the effects of BUP and ME. These results suggest that DA is involved in the abilities of ME and BUP to promote ambulation in mice.
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  • Yoshihiro Kiura, Ryosuke Hanaya, Tadao Serikawa, Kaoru Kurisu, Norio S ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 137-144
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    Noda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A and B neurons, according to the responses to a single stimulation of mossy fibers. In group A neurons, a stimulus elicited a long-lasting depolarization shift accompanying repetitive firings followed by after-hyperpolarization. In group B neurons, the same stimulus elicited a single spike without a long-lasting depolarization shift. Bath application of 1 mM Cd2+, a nonselective Ca2+ channel blocker, completely inhibited the abnormal excitation in group A neurons. We further examined the character of Ca2+ spikes in NER CA3 neurons. Ca2+ spikes were completely blocked by 10 μM Cd2+ in group A neurons, but not in either group B or control neurons, suggesting that Ca2+ channels in NER group A neurons have the hypersensitivity to Cd2+. Analysis using subtype specific blockers of Ca2+ channel raised the possible involvement of T-type Ca2+ channels. These results suggest that Ca2+ channel dysfunction is involved in the abnormal excitability of CA3 pyramidal neurons and pathogenesis of epilepsy in NER.
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Short Communications
  • Takeshi Ioroi, Motohiro Yamamori, Keiko Yagi, Midori Hirai, Yumei Zhan ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 145-148
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The mitogen–activated protein (MAP) kinase pathways has been shown to be necessary for mitogen-stimulated proliferation, but its role in cell migration has not been fully understood. In this study, we investigated the possible contribution of signaling pathways through c-Jun in platelet-derived growth factor (PDGF)-BB directed cell migration in rat aortic vascular smooth muscle cells (VSMCs) infected with a recombinant adenovirus containing the dominant-negative c-Jun (Ad-DN-c-Jun). DN-c-Jun protein was expressed dose-dependently in VSMCs infected with Ad-DN-c-Jun. Expression of DN-c-Jun significantly inhibited VSMC migration induced by PDGF-BB. Our results provide the first evidence that signaling pathways through c-Jun participates in cell migration induced by PDGF-BB in addition to other MAP kinase pathways in VSMCs.
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  • Mi-Hyeon Jang, Hyun-Kyung Chang, Min-Chul Shin, Taeck-Hyun Lee, Young- ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 149-152
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    Aqueous extracts of Ginseng radix have traditionally been used in the treatment of diabetes mellitus. In the present study, the effect of Ginseng radix on c-Fos expression in the hippocampus of streptozotocin (STZ)-induced diabetic rats was investigated via immunohistochemistry. Decreased c-Fos expression in the CA regions of the hippocampus was observed in STZ-induced diabetes, and administration of Ginseng radix enhanced the STZ-induced inhibition of c-Fos expression both dose- and duration-dependently. These results suggest that hyperglycemia-induced suppression of Fos expression may trigger the diabetes-induced disruption of hippocampal information processing and that Ginseng radix may alleviate this diabetes-induced disturbance in hippocampal functions.
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  • Tadashi Shimoyama, Shinsaku Fukuda, Qiang Liu, Yoshihiro Fukuda, Shige ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 153-157
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The aim of this study was to characterize the effects of rebamipide on the oxidative burst of human neutrophils. The neutrophil oxidative burst was measured in the presence of rebamipide and cimetidine using lucigenin- or luminol-dependent chemiluminescence (LgCL or LmCL). Rebamipide inhibited the LmCL response stimulated with opsonized zymosan, 12-myristate 13-acetate phorbol, and calcium ionophore in a dose-dependent manner, but the LgCL response was inhibited when neutrophils were stimulated with opsonized zymosan. LmCL response was also dose-dependently attenuated by rebamipide even in the presence of cimetidine. Thus, addition of rebamipide to H2-receptor antagonists can be considered for the treatment of gastric mucosal injury associated with oxidative stress.
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  • Hiroaki Kaji, Masahiko Kawada, Akihiro Tai, Hiroshi Kanzaki, Itaru Yam ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 158-162
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    Bursaphelenchus xylophilus (B. xylophilus) is a pine wood nematode that is known to cause pine wilt disease. We report here that B. xylophilus extracts augmented the polyclonal immunoglobulin E (IgE) production induced by lipopolysaccharide (LPS) plus interleukin-4 (IL-4) both in murine splenocytes and purified B cells as determined by ELISA and ELIspot assays, but they did not cause such a promotion in the absence of either LPS or IL-4. We also observed that the antigen-nonspecific IgE levels were increased in sera of mice treated with B. xylophilus extracts, which were comparable to those of Ascaris suum extracts. These findings suggest that administration of B. xylophilus extracts could suppress allergic diseases via a saturation of mast cell Fcε receptors or/and an inhibition of antigen-specific IgE synthesis to the allergen by a polyclonal response.
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  • Hideki Dohmoto, Akira Takahara, Hisayuki Uneyama, Ryota Yoshimoto
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 163-166
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    The Ca2+ channel-blocking efficacy of the cyproheptadine derivative AH-1058 (4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride) was quantitatively assessed using isolated guinea pig cardiomyocytes. AH-1058 (0.001 – 10 μM) and its mother compound cyproheptadine (1 – 100 μM) reduced the Ca2+ currents elicited from the holding potential of −80 or −40 mV. The IC50 values for cyproheptadine at holding potentials of −80 and −40 mV were 42.44 and 7.75 μM, respectively, whereas those for AH-1058 were 4.91 and 0.32 μM, respectively, whose potency was equivalent to those of the typical Ca2+ channel blocker verapamil. These results suggest that the introduction of the cinnamil structure to cyproheptadine can generate a potent L-type Ca2+ channel-blocking compound as potent as verapamil.
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Rapid Communication
  • Hong-Wei Zhang, Yuko Iida, Tsugunobu Andoh, Hiroshi Nojima, Jun Murata ...
    Subject area: Infomation Science
    2003 Volume 91 Issue 2 Pages 167-170
    Published: 2003
    Released: February 20, 2003
    JOURNALS FREE ACCESS
    Melanoma inoculation induced marked mechanical allodynia and hyperalgesia in the periphery of the melanoma mass in mice from about day 10 post-inoculation. In the middle of the tumor, there were slight hyperalgesia and response disappearance in the early and late phases, respectively. PGP9.5-like immunoreactivities increased in the epidermis of the periphery of the tumor and disappeared from the dermis of the middle on day 18 post-inoculation, without apparent alterations on day 10. When using this pain model, one should consider the tumor site-dependent responses.
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