All issues
Successor
Volume 87 (2001)
- Issue 4 Pages 245-
- Issue 3 Pages 171-
- Issue 2 Pages 97-
- Issue 1 Pages 1-
Volume 87, Issue 3
Displaying 1-12 of 12 articles from this issue
- |<
- <
- 1
- >
- >|
Reviews
-
Hisayuki Ohata, Ken-ichi Tanaka, Naoto Maeyama, Tadahiro Ikeuchi, Aya ...Subject area: Infomation Science
2001 Volume 87 Issue 3 Pages 171-176
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSThe mechanotransduction mechanism is believed to play an important role in maintenance of cellular homeostasis in a wide variety of cell types. In particular, the mechanotransduction system in vascular endothelial cells may be an essential mechanism for local hemodynamic control. Elevations in intracellular free Ca2+ concentration ([Ca2+]i) are an important signal in the initial step of mechanotransduction and mechanosensitive (MS) cation channels are thought to be a putative pathway; however, the molecular mechanisms remain unclear. We found that lysophosphatidic acid (LPA), a bioactive phospholipid, sensitizes the response of [Ca2+]i to mechanical stress in several cell types. Employing real-time confocal microscopy, local increases in [Ca2+]i in several regions within the cell during application of mechanical stress were clearly visualized in bovine lens epithelial and endothelial cells in the presence of LPA. The phenomenon was termed “Ca2+ spots”. Pharmacological studies revealed that Ca2+ spots arise due to influx through MS channels. In this report, our data indicating the possible significance of LPA as an endogenous factor involved in regulation of mechanotransduction is reviewed. Furthermore, our findings suggest that the Ca2+ spot is a novel phenomenon occurring as an elementary Ca2+-influx event through MS channels directly coupled with the initial step in mechanotransduction.View full abstractDownload PDF (1733K) -
Toshihiro Okamoto, Kazunori Kajino, Okio HinoSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 177-180
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSInterferon (IFN)-based therapy is a standard treatment for chronic hepatitis caused by hepatitis C virus (HCV) infection. This treatment is effective in approximately 30 – 40% of the patients and using ribavirin in combination with IFN increases the rate of sustained virologic clearance. For the remaining patients, glycyrrhizin is often used. Glycyrrhizin is known to prevent the development of hepatocellular carcinoma (HCC), but glycyrrhizin is usually administered intravenously. Drugs that are effective by oral administration are convenient for patients for long-term administration, and development of more effective drugs than glycyrrhizin is preferable. However, studies on drugs for the treatment of hepatitis are not actively conducted, and promotion of the study of drugs in this area is encouraging. For that reason, we show our approach to study drugs for the treatment of hepatitis. We analyzed the effect of glycyrrhizin on hepatitis as a standard chemical using the mouse liver injury model. Based on this, we screened drugs and found that a coumarin derivative seems to be one of model chemicals for the treatment of hepatitis.View full abstractDownload PDF (107K)
Full Papers
-
Hideki Amano, Kao Ando, Satoshi Minamida, Izumi Hayashi, Michiko Ogino ...Subject area: Infomation Science
2001 Volume 87 Issue 3 Pages 181-188
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSWe previously reported that endogenous prostaglandins (PGs) may increase cAMP facilitated angiogenesis through the induction of vascular endothelial growth factor (VEGF) in rat sponge implantation models. In the present experiment, we tested whether or not adenylate cyclase / protein kinase A (AC/PKA)-dependent VEGF induction enhanced angiogenesis in this model. Topical daily injections of 8-bromo-cAMP enhanced angiogenesis in a dose-dependent manner. Forskolin, an activator of AC, also facilitated angiogenesis as did amrinone, an inhibitor of phosphodiesterase. VEGF induction was confirmed by the increased levels in the fluids in the sponge matrix after topical injection of 8-bromo-cAMP. Immunohistochemical investigation further revealed the VEGF-expressed cells in the sponge granulation tissues to be fibroblasts, and the intensity of positive reactions was enhanced by 8-bromo-cAMP, forskolin and amrinone. Angiogenesis without topical injections of the above compounds was suppressed by SQ22,536, an inhibitor for AC, or H-89, an inhibitor for PKA, with concomitant reductions in VEGF levels. Daily topical injections of neutralizing antibody or anti-sense oligonucleotide against VEGF significantly suppressed angiogenesis. PGE2-induced angiogenesis was suppressed with SQ22,536 or H-89. These results suggested that AC/PKA-dependent induction of VEGF certainly enhanced angiogenesis and that pharmacological tools for controlling this signaling pathway may be able to facilitate the management of conditions involving angiogenesis.View full abstractDownload PDF (884K) -
Mamunur Rashid, Masatomo Watanabe, Mikio Nakazawa, Takashi Nakamura, K ...Subject area: Infomation Science
2001 Volume 87 Issue 3 Pages 189-194
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSThis study investigated the binding affinities of a newly synthesized 5-HT2 antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) for [3H]ketanserin bindings to 5-HT2 receptors in the rabbit cerebral cortex membranes using the radioligand binding assay method. The affinity of this compound was also compared with other 5-HT2-selective antagonists such as ketanserin, sarpogrelate, cyproheptadine and ritanserin, and the results showed that AT-1015 has a high pKi value for the 5-HT2 receptor. The rank order of these antagonists are: ritanserin > ketanserin ≅ AT-1015 > cyproheptadine ≅ sarpogrelate. We also evaluated the dissociation ability (slow or rapid) of AT-1015 in the rabbit cerebral cortex membrane and compared it with other 5-HT2 antagonists using the radioligand binding assay method. The blockade of [3H]ketanserin binding sites in the rabbit cerebral cortex induced by ketanserin and sarpogrelate was readily reversed by washing, whereas the inhibition by AT-1015, cyproheptadine and ritanserin was not readily reversed by washing. The % of control after washing are 76.10% and 49.55% for AT-1015 at 10−7.5 and 10−7.0 M, 67.32% and 50.17% for cyproheptadine at 10−7.5 and 10−7.0 M, and 72.38% and 39.80% for ritanserin at 10−9.5 and 10−9.0 M concentrations, respectively. Thus, these findings suggest that AT-1015 has antagonistic properties towards the 5-HT2 receptor and also shows that AT-1015 slowly dissociates from the 5-HT2 receptor, whereas, ketanserin and sarpogrelate dissociate rapidly from the 5-HT2 receptor, which do not correlate with their affinity.View full abstractDownload PDF (235K) -
Ken Arai, Norio Matsuki, Yuji Ikegaya, Nobuyoshi NishiyamaSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 195-201
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSIt is well demonstrated that acute or chronic stress leads to reduction of learning ability. Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, induces profound physiological and behavioral changes, including fever, decrease in food motivation, and decrease in social behavior. These changes might be interpreted as an acute stress reaction to the LPS. In the present study, therefore, we investigated the effects of LPS (400 – 800 μg/kg, i.p.) on spatial learning performances using C57BL/6J male mice. In the Morris water-maze task, spatial learning performances were examined in six trials of training for two consecutive days. LPS-treated mice took a longer time to reach the hidden platform than control mice (F(1,60) = 4.80801, P<0.05 at 600 μg/kg). In addition, injection of LPS decreased the percent of correct choices in the Y-maze test (P<0.05 at 800 μg/kg). LPS, however, did not alter the body weight, grip tone, motor activity or swimming speed. Taken together, these results indicate that LPS treatment specifically impaired spatial learning performances.View full abstractDownload PDF (234K) -
Shigeru Yoshida, Mizuko Yoshimura, Kohtaro TaniyamaSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 202-207
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSElectrophysiological properties of Xenopus oocytes exposed to alkaline extracellular pH (pHo) were investigated by measuring whole-cell currents using the two-electrode voltage-clamp method. Alkaline pHo (8.5 – 10.5) elicited an outward current in a pHo-dependent manner with a concomitant increase in the membrane conductance. This outward-current response was dependent on K+ because it was suppressed by a K+ channel blocker tetraethylammonium+ (20 mM), and the reversal potential of the response was in good agreement with the Nernst equation for K+. The response was not affected by pretreatment of oocytes with the acetoxymethyl ester of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 μM), a membrane-permeant intracellular Ca2+ chelator, but it was augmented by forskolin (0.4 μM), a stimulant of adenylate cyclase. The outward-current response originates in the oocyte but not in the surrounding follicle cells because the current could still be evoked when follicle cells were removed by collagenase or when gap junctions connecting the oocyte membrane and follicle cells were blocked by 1-octanol (1 mM). It is concluded that the outward current elicited by alkaline pHo in Xenopus oocytes is dependent on the activation of K+ channels via the cAMP pathway and that the outward current originates in the oocyte rather than the surrounding follicle cells.View full abstractDownload PDF (160K) -
Tomio Okamura, Hideyuki Fujioka, Kazuhide AyajikiSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 208-213
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSEffects of calcium antagonists on nitrergic nerve function were examined in the isolated canine corpus cavernosum. In the cavernous strips precontracted with phenylephrine, transmural electrical stimulation elicited frequency-dependent (2 – 5 Hz) relaxations that were abolished by NG-nitro-L -arginine (10−5 M), a nitric oxide (NO) synthase inhibitor; 1H[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10−6 M), a soluble guanylate cyclase inhibitor; and tetrodotoxin (3 × 10−7 M). The relaxations were not affected by treatment with nifedipine or nicardipine (10−8 – 10 −6 M), L-type specific calcium channel inhibitors, but were significantly inhibited by amlodipine or cilnidipine, inhibitors of L- plus N-type calcium channels, in a concentration-related manner (10−7 – 10 −6 M). All of the inhibitors used did not affect the relaxations induced by exogenous NO (acidifed NaNO2). These findings suggest that N-type, but not L-type, calcium channels are responsible for increasing cytosolic free calcium, a prerequisite for the synthesis of NO, in the nitrergic dilator nerves innervating the corpus cavernosum.View full abstractDownload PDF (204K) -
Tsuneo Yasuda, Keiichiro Okamoto, Takeshi Iwamoto, Shinya Miki, Norihi ...Subject area: Infomation Science
2001 Volume 87 Issue 3 Pages 214-225
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSWe studied the effects of OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo [1,5-a]pyrimidine), a novel analgesic compound, on the inhibitory action of adenosine on the contraction of guinea pig ileum and investigated the effects of OT-7100 on the nociceptive responses in animal models of inflammatory and peripheral neuropathic hyperalgesia and decreases spinal c-Fos expression. OT-7100 at 0.3 – 3 μM significantly enhanced the inhibitory effect of adenosine on the contraction of guinea pig ileum. The efficacy of OT-7100 (1, 3 or 10 mg/kg, p.o.) on hyperalgesia induced by yeast or substance P and in the Bennett model was significantly suppressed by coadministration of the adenosine A1 antagonist DPCPX (0.01 or 0.1 pmol/animal, i.t.), while OT-7100 without DPCPX significantly increased the nociceptive threshold in each rat model. OT-7100 (3, 10 and 30 mg/kg per day, p.o.) significantly inhibited the mechanical nociceptive threshold in the injured paw in the Chung model. OT-7100 (30 mg/kg, p.o.) significantly decreased the number of Fos-LI neurons in the spinal dorsal horn in the Bennett model. These finding suggest that OT-7100 inhibits hyperalgesia in these animal models possibly by enhancing adenosinergic neurotransmission in the dorsal horn, although we still lack direct evidence for it.View full abstractDownload PDF (562K) -
Kenichi Shimada, Tomoyuki Abe, Mitsunobu Mio, Chiaki KameiSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 226-230
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSThe influence of the protein kinase A (A kinase) system in differentiation of HL-60-Eo cells to eosinophils induced by histamine was studied. Although 8-Cl-cAMP caused inhibitions of proliferation and [3H]thymidine uptake of HL-60-Eo cells similarly to histamine, no significant eosinophilic differentiation was observed. Histamine as well as 8-Cl-cAMP caused elevation of A kinase activity. However, KT-5720, an inhibitor of A kinase, had no effect on histamine-induced eosinophil differentiation. RIα antisense oligodeoxynucleotide caused significant inhibition of HL-60-Eo cell growth, but RIIβ antisense oligodeoxynucleotide had no effect. On the other hand, neither of the antisense oligodeoxynucleotides showed potentiating effects on growth inhibition induced by histamine. In addition, RIα and RIIβ antisense oligodeoxynucleotides caused neither differentiation to eosinophils itself nor potentiation of histamine-induced differentiation. From these findings, it was concluded that A kinase is not correlated directly with differentiation of HL-60-Eo cells to eosinophils.View full abstractDownload PDF (329K)
Short Communications
-
Takehiro Hagiwara, Sumie Satoh, Yoshio Kasai, Kiyoshi TakasunaSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 231-234
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSWe examined the effects of ten fluoroquinolone antibacterial agents, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin, tosufloxacin, gatifloxacin, grepafloxacin, moxifloxacin and sparfloxacin, on action potentials recorded from guinea pig ventricular myocardia. Sparfloxacin prolonged action potential duration (APD) by about 8% at 10 μM and 41% at 100 μM. Gatifloxacin, grepafloxacin and moxifloxacin also prolonged APD at 100 μM by about 13%, 24% and 25%, respectively. In contrast, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin and tosufloxacin had little or no APD-prolonging effect at concentrations as high as 100 μM. These findings suggest that there are differences in potency to prolong QT interval among the fluoroquinolones.View full abstractDownload PDF (178K) -
Toshitsugu Ogura, Sunao Imanishi, Toshishige ShibamotoSubject area: Infomation Science
2001 Volume 87 Issue 3 Pages 235-239
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSThe effects of the tyrosine kinase (TK) inhibitor tyrphostin A23 and its inactive analog tyrphostin A1 on background membrane conductance were investigated in guinea pig ventricular myocytes. TK-inhibiting A23 reversibly increased membrane conductance under conditions designed to minimize Na+, Ca2+, K+, and Na+-K+ pump currents. Similar stimulatory action was obtained with TK-inactive A1. The tyrphostin-induced current was inhibited by omitting external Na+ or Ca2+, suppressed by chelating internal Ca2+, blocked by external Cd2+ and Ni2+, and insensitive to changes in internal Cl− concentration. We conclude that tyrphostins have a direct, TK-independent action that increases membrane conductance probably by stimulating Na+-Ca 2+ exchange.View full abstractDownload PDF (190K) -
Yoshimasa Yamaguchi, Masaya Higashi, Toshiyuki Matsuno, Seiichiro Kawa ...Subject area: Infomation Science
2001 Volume 87 Issue 3 Pages 240-244
Published: 2001
Released on J-STAGE: November 20, 2001
JOURNAL FREE ACCESSEffects of ZSET845 (3,3-dibenzylimidazo[1,2-a]pyridin-2-(3H)-one), a newly synthesized cognitive enhancer, and donepezil and tacrine on the scopolamine-induced cognitive deficits in rats were examined in passive avoidance and radial-arm maze tasks. ZSET845 (0.01 mg/kg) showed a greater ameliorative effect than donepezil (0.1 mg/kg) or tacrine (1 mg/kg) in the passive avoidance task. In the radial-arm maze task, ZSET845 (0.1 mg/kg) also showed a greater effect than donepezil (10 mg/kg) or tacrine (10 mg/kg). ZSET845 induced an increase in the choline acetyltransferase (ChAT) activity in the hippocampus, suggesting that the ameliorative effects of ZSET845 are related to the increase in the ChAT activity in the hippocampus.View full abstractDownload PDF (329K)
- |<
- <
- 1
- >
- >|