Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Volume 99 , Issue 1
Showing 1-15 articles out of 15 articles from the selected issue
Current Perspective
  • Akira Nakajima, Ya-Ping Tang
    2005 Volume 99 Issue 1 Pages 1-5
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    Learning and memory is an essential component of human intelligence. To understand its underlying molecular and neuronal mechanisms is currently an extensive focus in the field of cognitive neuroscience. We have employed advanced mouse genetic approaches to analyze the molecular and neuronal bases for learning and memory, and our results showed that brain region-specific genetic manipulations (including transgenic and knockout), inducible/reversible knockout, genetic/chemical kinase inactivation, and neuronal-based genetic approach are very powerful tools for studying the involvements of various molecules or neuronal substrates in the processes of learning and memory. Studies using these techniques may eventually lead to the understanding of how new information is acquired and how learned information is memorized in the brain.
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Survery Review
  • Marie Eve Moreau, Nancy Garbacki, Giuseppe Molinaro, Nancy J. Brown, F ...
    2005 Volume 99 Issue 1 Pages 6-38
    Published: 2005
    Released: September 22, 2005
    JOURNALS FREE ACCESS
    The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.
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Full Papers
  • Sibel Silici, Nedret A. Koç, Demet Ayangil, Soner Çankay ...
    2005 Volume 99 Issue 1 Pages 39-44
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    Yeasts isolated from patients with superficial mycoses were tested against propolis samples collected from different regions and honeybee races. The minimum inhibitory concentration (MIC) values obtained using the agar dilution methods were compared to the diameters of growth inhibition zones by using the disk diffusion method. The results showed that Candida albicans, C. glabrata, Trichosporon spp., and Rhodotorula sp. were susceptible to low concentrations of propolis, the latter showing a higher susceptibility. Relative to the other propolis tested, the propolis sample collected by Apis mellifera caucasica possessed the highest antifungal activity against all of the superficial mycoses. In contrast, the propolis samples collected by A.m. carnica and A.m. anatolica were the least active samples. Also, the propolis sample from the Adana region is more active than samples from other regions. An increase of MIC values was accompanied by a decrease of growth inhibition zone diameters.
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  • Yasuhiro Takagi, Takashi Omura, Minoru Yoshiyama, Ryo Matsumoto, Soich ...
    2005 Volume 99 Issue 1 Pages 45-51
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: August 26, 2005
    JOURNALS FREE ACCESS
    Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 × 107 cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues.
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  • Yurika Kino, Mitsuo Tanabe, Motoko Honda, Hideki Ono
    2005 Volume 99 Issue 1 Pages 52-60
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: August 26, 2005
    JOURNALS FREE ACCESS
    The neuronal pathways involved in the muscle relaxant effect of tizanidine were examined by measurement of spinal reflexes in rats. Tizanidine (i.v. and intra-4th ventricular injection) decreased the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR and DSR, respectively) in non-spinalized rats. Depletion of central noradrenaline by 6-hydroxydopamine abolished the depressant effect of tizanidine on the MSR almost completely and attenuated the effect on the DSR. Co-depletion of serotonin by 5,6-dihydroxytryptamine and noradrenaline resulted in more prominent attenuation of tizanidine-induced inhibition of the DSR. Supraspinal receptors were then studied using yohimbine- and some imidazoline-receptor ligands containing an imidazoline moiety. Idazoxan (I1, I2, I3, and α2), efaroxan (I1, I3, and α2), and RX821002 (I3 and α2), but not yohimbine, an α2-adrenergic receptor antagonist with no affinity for I receptors, antagonized the inhibitory effects of tizanidine. Thus, supraspinal I receptors (most likely I3) and descending monoaminergic influences are necessary for tizanidine-induced inhibition of spinal segmental reflexes.
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  • Mitsuo Mita, Michael P. Walsh, Masaki Saito
    2005 Volume 99 Issue 1 Pages 61-67
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: August 26, 2005
    JOURNALS FREE ACCESS
    We previously reported the relationship between α1-adrenoceptor-mediated contraction and phosphorylation of 20-kDa myosin light chain (LC20) in de-endothelialized rat caudal arterial smooth muscle at room temperature (Mita M, Walsh MP. Biochem J. 1997;327:669-674). We now describe the effect of increasing the temperature to 37°C on this relationship. The EC50 value (76.6 ± 18.2 nM) for cirazoline (α1-adrenergic agonist)-induced contraction of the strips at room temperature (23°C) was significantly greater than that (14.5 ± 1.9 nM) at 37°C. The initial rate of the contraction to a sub-maximal concentration of cirazoline (0.3 μM) was similar at the two temperatures. However, cirazoline-induced maximal force at 37°C was approximately 1.8 times that at room temperature. LC20 phosphorylation in response to cirazoline at room temperature and 37°C closely matched the time courses of contraction, but values were not significantly different at the two temperatures: resting phosphorylation levels were 0.09 ± 0.04 mol Pi/mol LC20 at 37°C and 0.22 ± 0.06 mol Pi/mol LC20 at room temperature; maximal cirazoline-stimulated LC20 phosphorylation levels were 0.58 ± 0.08 mol Pi/mol LC20 at room temperature and 0.49 ± 0.05 mol Pi/mol LC20 at 37°C. We conclude, therefore, that the enhanced cirazoline-induced contraction at 37°C is not due to increased LC20 phosphorylation.
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  • Chin-Cheng Lee, Yi-Yang Lee, Cheng-Kuei Chang, Mao-Tsun Lin
    2005 Volume 99 Issue 1 Pages 68-76
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: August 26, 2005
    JOURNALS FREE ACCESS
    The aim of the present study was to determine whether the possible occurrence of renal ischemia and damage during heatstroke can be suppressed by prior administration of L-N6-(1-iminoethyl) lysine (L-NIL), a selective inducible nitric oxide synthase (iNOS) inhibitor. Urethane-anesthetized rats were exposed to heat stress (43°C) to induce heatstroke. Control rats were exposed to 24°C. Mean arterial pressure and renal blood flow after the onset of heatstroke both were significantly lower in vehicle-treated heatstroke rats than in normothermic controls. However, both the body temperature and renal damage scores were greater in vehicle-treated heatstroke rats compared with normothermic controls. Plasma nitric oxide (NO), creatinine, and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite all were significantly higher in vehicle-treated heatstroke rats compared with their normothermic controls. Pretreatment with L-NIL (3 mg/kg, administered intravenously and immediately at the onset of heat stress) significantly attenuated heatstroke-induced hyperthermia, arterial hypotension, renal ischemia and damage, increased renal levels of immunoreactivity of iNOS and peroxynitrite, and increased plasma levels of NO, creatinine, and BUN. Accordingly, pretreatment with L-NIL significantly improved survival during heatstroke. The results suggest that selective inhibition of iNOS-dependent NO and peroxynitrite formation protects against renal ischemia and damage during heatstroke by reducing hyperthermia and arterial hypotension.
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  • Motomu Tanaka, Kei Maruyama
    2005 Volume 99 Issue 1 Pages 77-82
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: August 26, 2005
    JOURNALS FREE ACCESS
    Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 μM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean ± S.E.M.: 8.85 ± 1.60 and 10.40 ± 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 μl in total in 10 aliquots of 2 μl at 30-s intervals) induced 27.29 ± 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 ± 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg/kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer non-myelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Aδ-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Aδ-fibers.
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  • Yong-Wook Shin, Dong-Hyun Kim
    2005 Volume 99 Issue 1 Pages 83-88
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    The antipruritic and vascular permeability-inhibitory effects of ginsenoside Rb1, a main component of ginseng frequently used as a traditional medicine in Asian countries, and its metabolite compound K by intestinal microflora were investigated in scratching behavior animal models induced by compound 48/80, substance P, and histamine. Ginsenoside Rb1 and compound K orally administered 1 and 6 h before the treatment of compound 48/80 showed antipruritic effect. These ginsenosides administered at a dose of 50 mg/kg 6 h before the treatment of compound 48/80 inhibited scratching behaviors by 51% and 64%, respectively, compared with that of the control. These ginsenosides also inhibited the vascular permeability of skin. Compound K intraperitoneally administered 1 h before the treatment of compound 48/80 potently inhibited the scratching behaviors induced by compound 48/80. However, intraperitoneally administered ginsenoside Rb1 did not inhibit scratching behaviors. Compound K inhibited compound 48/80-, substance P-, and histamine-induced scratching behaviors, with 50% inhibitory doses of 4.2, 5.9, and 3.8 mg/kg, respectively, and vascular permeability, with 50% inhibitory doses of 5.8, 6.8, and 4.1 mg/kg, respectively. These results suggest that ginsenoside Rb1 and its metabolite compound K by intestinal microflora can improve scratching behaviors.
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  • Kazuhiro Tamura, Yusuke Suzuki, Hirotake Hashiba, Hiroshi Tamura, Sumi ...
    2005 Volume 99 Issue 1 Pages 89-94
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    The present study was undertaken to determine the effects of etidronate (ED) on calcitriol-induced aortic calcification and bone metabolism in rats with renal failure. Severe aortic calcification was induced by treatment with calcitriol for 3 weeks in rats in which 5/6 of the kidneys were removed (SNx group). Treatment of ED (10 mg/kg) together with calcitriol after subtotal nephrectomy (SNx) significantly inhibited thoracic and abdominal aortic calcification 3 weeks after the operation; however, ED (2 mg/kg) was ineffective. The serum levels of osteocalcin and pyridinoline decreased in ED (10 mg/kg) treated-renal failure rats compared with SNx rats. Total bone mineral density (BMD) in the SNx group was lower than that in the sham group, in which animals were treated with calcitriol after a sham operation. The total BMD value in the ED (10 mg/kg)-treated group was similar to that in the SNx group, whereas the levels of cancellous BMD were low in the ED (10 mg/kg)-treated rats. Our data show that ED at a dosage that suppresses bone metabolism markedly inhibits vascular calcification in rats with renal failure.
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  • Yuji Kawahara, Kouichi Tanonaka, Takuya Daicho, Mikio Nawa, Ryo Oikawa ...
    2005 Volume 99 Issue 1 Pages 95-104
    Published: 2005
    Released: September 22, 2005
    JOURNALS FREE ACCESS
    Ketamine and xylazine are routinely used for measurement of hemodynamics of mice and rats by echocardiography. The anesthetic agents produce low heart rate (HR) in the animals, which may result in misleading data in the hemodynamic profiles of the small animals. The purpose of the present study was to select an appropriate anesthetic condition in the evaluation of mouse and rat cardiac function by echocardiography. Echocardiographic measurement was performed in male C57BL6 mice anesthetized with an intraperitoneal injection of 30 or 40 mg/kg pentobarbital (P30 or P40) or a combination of 60 mg/kg ketamine and 6 mg/kg xylazine (KX) and in male Wistar rats with an intraperitoneal injection of 40 or 50 mg/kg pentobarbital (P40 or P50) or a combination of 100 mg/kg ketamine and 10 mg/kg xylazine (KX). Basal HR of P30-anesthetized mice and P40-anesthetized were comparable to those in the conscious state, whereas KX-anesthetized mice and rats were 38% and 74% of those of the conscious animals, respectively. Fractional shortening (FS) and cardiac output index (COI) of the P30-anesthetized mice or the P40-anesthetized rats were greater than those of KX-anesthetized animals. Intraperitoneal injection of dobutamine at 0.3 and 1 mg/kg increased HR, FS, and COI of the P30-anesthetized mice and the P40-anesthetized rats, respectively, whereas the percent responses of these parameters in KX animals were greater than those in pentobarbital-anesthetized ones due to the lower basal values for the cardiac functional parameters. Anesthesia with P30 for the mouse and P40 for the rat rather than ketamine/xylazine may be relevant to the evaluation of cardiac function using echocardiography.
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Short Communications
  • M. Helena Vasconcelos, Luis F. Maia, Cristina Sousa, Sandra S. Beleza, ...
    2005 Volume 99 Issue 1 Pages 105-108
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    In order to be active, antisense oligonucleotides (ASOs) should be delivered to the nuclei of cells. The lack of effect of some ASOs might be explained by poor distribution inside the cell. Here we describe the study of the intracellular distribution of an ASO in a leukemic cell line in which the ASO was not showing an effect. We used fluorescein isothiocyanate-labeled ASO and fluorescent or confocal microscopy. The internalised ASO was localized in a specific intracellular juxtanuclear region, showing no cytoplasmic or nuclear diffusion. Transfection of the ASO improved cellular distribution to the cytoplasm and nuclei and improved the ASO effect.
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  • Radan Stojanovic, Zoran Todorovic, Zorica Nesic, Sonja Vuckovic, Milic ...
    2005 Volume 99 Issue 1 Pages 109-112
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 Hz) and aminophylline (AMPh) pretreatment on the effect of NG-nitro-L-arginine methyl ester (L-NAME) (1 mM) on isolated rat diaphragm was investigated. L-NAME potentiated tension developed (Td) in the diaphragm pretreated with a single concentration of AMPh (1.08 mM) in a frequency-dependent manner. The effect was significantly different in comparison with muscle incubated 30 min with Tyrode solution only. In the muscle pretreated with cumulative concentrations of AMPh (0.36 - 3.60 mM), the frequency-dependent potentiation of Td induced by L-NAME and the difference between L-NAME-treated and untreated muscle were lost.
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  • Takuji Machida, Miho Hiramatsu, Naoya Hamaue, Masaru Minami, Masahiko ...
    2005 Volume 99 Issue 1 Pages 113-116
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    The effect of docosahexaenoic acid (DHA) on cyclooxygenase expression induced by interleukin (IL)-1β and phorbol 12-myristate 13-acetate (PMA) in rat vascular smooth muscle cells (VSMCs) was investigated in order to clarify the cellular mechanism of cardiovascular protective effects. DHA and eicosapentaenoic acid slightly enhanced IL-1β-induced cyclooxygenase (COX)-2, but not COX-1, expression, whereas arachidonic acid had no effect. DHA also slightly enhanced PMA-induced COX-2 expression. DHA stimulated both rapid and prolonged activation of p44/42, but not p38, mitogen-activated protein kinase (MAPK) induced by IL-1β and PMA. These results suggest that DHA enhances the COX-2 expression by selectively facilitating p44/42 MAPK activation in VSMCs.
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  • Eun-Joo Shin, Jin Hyeong Jhoo, Toshitaka Nabeshima, Wang-Kee Jhoo, Myu ...
    2005 Volume 99 Issue 1 Pages 117-120
    Published: 2005
    Released: September 22, 2005
    [Advance publication] Released: September 01, 2005
    JOURNALS FREE ACCESS
    Accumulating evidence indicates that growth hormone (GH) might be effective at preventing the development of Alzheimer’s disease. However, exogenous GH treatment has exhibited side effects for clinical application; thus supplementation with amino acids to promote the release of GH could be a possible alternative treatment. In this study, mice that were fed with a diet of GH-releasing supplements had significantly attenuated memory impairments and hippocampal changes in the acetylcholinesterase activity and acetylcholine level induced by amyloid beta protein (Aβ) (1 – 42). Our results suggest that the use of GH-releasing supplement exerts beneficial effects on the memory impairment induced by Aβ (1 – 42).
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