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Volume 85 (2001)
- Issue 4 Pages 339-
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Volume 85, Issue 2
Displaying 1-13 of 13 articles from this issue
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Review
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Yoshiaki TabuchiSubject area: Infomation Science
2001 Volume 85 Issue 2 Pages 117-123
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSIt has been indicated that transgenic mouse harboring a temperature-sensitive simian virus 40 large T-antigen gene is useful for establishing cell lines from tissues that have proved difficult to culture in vitro. The gastric surface mucous cell line GSM06 was established from a primary culture of gastric fundic mucosal cells of the transgenic mice. GSM06 cells showed temperature-sensitive growth in culture and expressed large T-antigen at a permissive temperature (33°C) but not at a nonpermissive temperature (39°C). At 39°C, the cells produced periodic acid-Schiff positive glycoconjugates that formed a mucous sheet like the gastric surface mucosa in the stomach. Insulin markedly increased the production of glycoconjugates. In addition, proprotein-processing endoprotease furin suppression retarded cell growth, but accelerated cell differentiation. An air-liquid interface promoted the differentiation of GSM06 cells in a reconstruction culture with nitrocellulose membrane and collagen gel. The gastric surface mucous cell line GSM06 with unique characteristics, therefore, should be useful as an in vitro model of the gastric mucosa for physiological and pharmacological investigations. Moreover, experiments using immortalized cells established in vitro and having specific functions may offer an alternative to experiments using living animals and thereby offer a solution to this ethical issue.View full abstractDownload PDF (154K)
Full papers
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Mitsutoshi Munakata, Kazuo Noguchi, Hiroaki Araki, Norio AkaikeSubject area: Infomation Science
2001 Volume 85 Issue 2 Pages 124-132
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSThe effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14-carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely dissociated rat neocortical neurons by using a nystatin-perforated patch recording configuration. VA activated a steady-state outward current in a concentration-dependent manner, with an EC50 of 0.65 μM. The reversal potential for the current shifted 56.5 mV with tenfold changes in the extracellular K+ concentration, suggesting that the current was carried by K+. The VA-induced current was not suppressed by apamin (1 μM), charybdotoxin (1 μM), Cs + (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10 μM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4 mM. These pharmacological properties of the VA-induced current were compatible with a slowly inactivating delayed rectifier current (IK). It was suggested that the current activated by VA was IK. The VA-induced current was not affected by Ca2+ depletion or by staurosporine (0.1 μM), quinacrine (10 μM), wortmanin (1 μM) or genistein (1 μM). The intracellular perfusion of GDPβS (0.4 mM) also had no significant effect. Thus, VA may directly activate the K+ channels.View full abstractDownload PDF (316K) -
Nitric Oxide Donating Compounds Inhibit HCl-Induced Gastric Mucosal Lesions Mainly via ProstaglandinMasayuki Uchida, Kei Matsueda, Ryosuke Shoda, Akira Muraoka, Shigeru Y ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 133-138
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSProstaglandin (PG) and nitric oxide (NO) have been known to inhibit the lesion formation induced by necrotic agents. However, no clear correlation between PG and NO has been shown in the gastroprotective action against necrotic agent-induced gastric mucosal lesions in rats. Thus, the present study was performed to clarify this correlation. Gastric mucosal lesions were induced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3 - 3 μg/kg, p.o.; dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 μg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotective action by dim-PGE2 was not affected by the pre-treatment with NG-nitro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO donating compounds inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of NO in rats.View full abstractDownload PDF (550K) -
Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in GlomeruliTadashi Nagamatsu, Toshiyuki Nagao, Jun-ichi Koseki, Masayuki Sugiura, ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 139-145
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSRecently we immunohistochemically demonstrated that prostaglandin E2 (PGE2) promoted the clearance of aggregated bovine serum albumin (a-BSA) deposited in glomeruli. Herein, we investigated the role of PGE2 and its signal transduction in the disposal of macromolecules in glomeruli. EP2 and EP4 receptor mRNA was detected in glomeruli by RT-PCR analysis. A-BSA was injected twice into mice. Glomeruli were then isolated and incubated. A-BSA gradually disappeared from isolated glomeruli. PGE2 increased the intracellular cyclic AMP and decreased a-BSA level in glomeruli. Additionally, 8-bromo-cyclic AMP evoked a loss of a-BSA in isolated glomeruli. The effect of 8-bromo-cyclic AMP on the clearance of a-BSA was abolished by KT 5720 in glomeruli. PGE2 and 8-bromo-cyclic AMP also prompted disposal of a-BSA in cultured mesangial cells. These findings indicate that PGE2 positively regulates the removal of macromolecules via cyclic AMP and protein kinase A in glomeruli, and they provide insight into how to prevent the development of glomerulonephritis and glomerulosclerosis.View full abstractDownload PDF (437K) -
Kazuyuki Ozaki, Tadashi Yamamoto, Takaharu Ishibashi, Taku Matsubara, ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 147-154
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSWe investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on endothelial vasoactive substances using human umbilical vein endothelial cells (HUVECs). Incubation of HUVECs with fluvastatin for 12 h increased endothelial nitric oxide synthase (eNOS) mRNA expression in a concentration-dependent manner (peak, 276 ± 38%, mean ± S.D., of the control, at 1.0 μM fluvastatin, P &0.01). In addition, fluvastatin increased eNOS protein production (245 ± 51% of the control level, P<0.05) as well as nitrite production (165 ± 35% of the control level, P<0.01). In contrast, incubation of HUVECs with 1.0 μM fluvastatin for 12 h significantly reduced the production of endothelin-1 (ET-1) and preproET-1 mRNA expression in HUVECs (28 ± 1% and 39 ± 1% of the control level, respectively, P <0.01). Our results suggest that fluvastatin might be involved in improvement of endothelial function and prevention of the progression of atherosclerosis.View full abstractDownload PDF (913K) -
Yusuke Hori, Jiro Hoshino, Chihiro Yamazaki, Tomoko Sekiguchi, Satoshi ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 155-160
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSChondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg/kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.View full abstractDownload PDF (282K) -
Tsutomu Sakuma, Mieko Hida, Yoshihiro Nambu, Kazuhiro Osanai, Hirohisa ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 161-166
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSBecause it was still uncertain whether a stimulation of β1-adrenoceptors accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of denopamine, a selective β1-adrenergic agonist, on alveolar fluid clearance was determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue labeled albumin instilled into the alveolar spaces over 1 h at 37°C in isolated rat lungs. The principle results were as follows: 1) Although lung water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of denopmaine was similar to that of terbutaline, a selective β2-adrenergic agonist. In summary, denopamine is a potent stimulator of alveolar fluid clearance in rats exposed to hyperoxia.View full abstractDownload PDF (144K) -
Uta Wethmar, Walter Raasch, Andreas Dendorfer, Peter DominiakSubject area: Infomation Science
2001 Volume 85 Issue 2 Pages 167-174
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSLigands for angiotensin II-(AT)-receptors and imidazoline receptors have structural similarities and influence blood pressure via various mechanisms. The goal of this study was to study the specificity of various ligands by displacement experiments. Antazoline, cimetidine, clonidine, efaroxan, guanabenz, guanethidine, idazoxan, moxonidine and rilmenidine up to a concentration of 100 μM failed to displace the specific binding of [125I]Sar1,Ile8 angiotensin II at the AT1-receptor characterized by losartan (IC50 = 26 ± 12 nM) in liver homogenate. The same substances up to 100 μM produced no reduction of specific [125I]Sar1,Ile8 angiotensin II binding to the AT2-receptor of phaeochromocytoma cell membranes characterized by PD123319 (IC50 = 20 ± 5 nM). Displacement experiments at the imidazoline I1-receptors were performed on bovine adrenal medulla membranes using [3H]clonidine after characterization by the I1-ligand clonidine (IC50 = 459 ± 13 nM) and the I2-ligand idazoxan (IC50 = 3.29 ± 0.88 μM). The investigated AT-receptor ligands angiotensin II, losartan, EXP 3174 and PD123319 revealed no displacement of [3H]clonidine up to a concentration of 100 μM. The I2-receptor in liver homogenate was characterized by displacement of [3H]idazoxan by cold idazoxan and clonidine (IC50 = 0.37 ± 0.17 and 68 ± 31 μM, respectively). The investigated AT-receptor ligands angiotensin II, losartan and PD123319 failed to displace [3H]idazoxan specifically up to 100 μM. Hence, the tested substances showed no cross-reactivity at the corresponding AT- and I-receptors up to 100 μM, a concentration markedly higher than the plasma concentrations achieved after therapeutic application.View full abstractDownload PDF (219K) -
Takehiro Ochi, Aiko Yamane-Sugiyama, Yoshitaka Ohkubo, Kazuo Sakane, H ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 175-182
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSThe anti-inflammatory and ulcerogenic effects of FR188582, 3-chloro-5-[4-(methylsulfonyl) phenyl]-1-phenyl-1H-pyrazole, were investigated. In a recombinant human cyclooxygenase (COX) enzyme activity, FR188582 inhibited COX-2 with an IC50 value of 0.017 μM, and the inhibition of prostaglandin (PG) E2 formation by FR188582 was over 6000 times more selective for COX-2 than COX-1. Oral administration of FR188582 dose-dependently inhibited adjuvant arthritis. This effect was threefold more potent than that of indomethacin. FR188582 and indomethacin dose-dependently suppressed the formation of immunoreactive PGE2, but not immunoreactive leukotriene (LT) B4, in arthritic paw. Unlike indomethacin, FR188582 did not induce visible gastric lesions in rats at doses up to 32 mg/kg, p.o. Furthermore, FR188582 did not inhibit the level of immunoreactive PGE2 and immunoreactive 6-keto PGF1α in rat gastric mucosa. These results suggest that FR188582, a highly selective COX-2 inhibitor, has a potent anti-inflammatory effect mediated by inhibition of PGE2 in inflamed tissues. The safety profile of FR188582 appears to be improved over the safety profile of indomethacin.View full abstractDownload PDF (432K) -
Huang Yi-Tsau, Lin Han-Chieh, Chang Yuan-Yi, Yang Ying-Ying, Lee Shou- ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 183-188
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSSynephrine, a sympathomimetic α1-adrenoceptor agonist, has been shown to induce dose-dependent portal hypotensive effects after acute intravenous infusion. The present study was undertaken to investigate the hemodynamic effects of 8-day administration of synephrine in portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL). Portal hypertensive rats were allocated into one of two groups: vehicle group (0.1 N HCl, 0.5 ml/12 h) or synephrine group (1 mg/kg per 12 h), with 7 rats in each group. Synephrine or vehicle was administered by gavage into PVL and BDL rats for 8 consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. Synephrine significantly ameliorated the hyperdynamic state in both PVL and BDL rats. The portal venous pressure in PVL and BDL rats (−13.5% and −10.1%, respectively), portal tributary blood flow (−19.5% and −20.4%) and cardiac index (−12.1% and −18.8%) were significantly reduced, while mean arterial pressure (10.4% and 23.4%) and systemic (26.3% and 51.0%) as well as portal territory (47.1% and 67.7%) vascular resistance were enhanced by treatment of synephrine as compared with vehicle treatment. Our results showed that eight-day administration of synephrine exerted beneficial hemodynamic effects in two models of portal hypertensive rats.View full abstractDownload PDF (106K) -
Taeko Hata, Hiroyuki Nishikawa, Eiji Itoh, Yoshinori FunakamiSubject area: Infomation Science
2001 Volume 85 Issue 2 Pages 189-196
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSTo clarify the relationship between SART (specific alternation of rhythm in temperature) stress (repeated cold stress) and anxiety, the effects of various types of stress on the behavior of mice were studied in elevated plus-maze tests and then the effects of anxiolytics were evaluated. The percentage of time spent in the open arms of the plus-maze apparatus decreased in mice subjected to SART stress without change in the total number of arm entries. No change was noted in mice subjected to other stresses, such as 1-h, 2-day and 5-day cold stress and 1-h, 15-h and 5 × 15-h restraint stress. The reduction in the percentage of time spent in the open arms caused by SART stress was inhibited by single and repeated administrations of diazepam and alprazolam and by a single administration of buspirone, which have no influence on the percentage of time spent in the open arms in nonstressed mice, but not by flumazenil, WAY-100635 and chronic treatment with buspirone. The effects of diazepam and buspirone were antagonized by flumazenil and WAY-100635, respectively. The behavior of SART-stressed mice in the plus-maze would thus appear to arise from anxiety, to which benzodiazepine and serotonin receptors are related, but the diazepam binding inhibitor, an endogenous anxiogenic protein, is not. Thus SART-stressed animals may be useful for investigating the psychopharmacological and neuropharmacological basis of anxiety.View full abstractDownload PDF (200K) -
Masaki Tabuchi, Keizo Umegaki, Tomohiro Ito, Motohisa Suzuki, Masahiko ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 197-202
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSMalignant stroke-prone spontaneously hypertensive rats (M-SHRSP), separated from SHRSP, develop severe hypertension and spontaneously develop stroke at early ages. Using this model of cerebrovascular stroke, influence of stroke-onset on the autonomic nervous system was investigated. Heart rate (HR), systolic and diastolic blood pressures (SBP and DBP) and locomotive activity were monitored during development of stroke using a telemetry system. Stroke-onset was assessed by neurologic symptoms, changes in body weight, fluid intake and serum NOx level. The rat displayed a nocturnal pattern of circadian rhythms. At stroke-onset, mean HR over 24 h increased by 20 to 30 bpm and rapidly increased at post stroke, approximately 100 bpm higher than that at pre stroke. Circadian variation in HR, which was normally 50 bpm higher during night than during day, attenuated at stroke-onset, and it was blunted or reversed at post stroke. BP variation, which was approximately 7 mmHg higher at night than at day, decreased one or two days before stroke-onset and reversed at post stroke, especially in DBP. Insufficient falls in HR and BP during the day mainly accounted for the disturbed circadian variations. Variation of locomotive activity also decreased. These changes serve as reliable and accurate markers for stroke-onset in evaluation of drugs for the prevention and outcome predictions of stroke.View full abstractDownload PDF (492K)
Short Communication
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Hideo Honda, Hiroko Moroe, Hiroyuki Fujii, Katsunori Arai, Yoko Notoya ...Subject area: Infomation Science
2001 Volume 85 Issue 2 Pages 203-206
Published: 2001
Released on J-STAGE: May 10, 2001
JOURNAL FREE ACCESSThe tension of isolated rings was measured isometrically to compare the NG-nitro-L-arginine- and indomethacin-resistant relaxation by acetylcholine (ACh) in the renal artery from normal rabbits and short term hypercholesterolemia rabbits (0.5% cholesterol chow for 5 weeks). ACh-induced relaxation in the renal artery precontracted with phenylephrine was not influenced by cholesterol-enriched chow. However, in comparison with artery from normal rabbits, the N G-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation by ACh was significantly enhanced by the chow. The resistant part of ACh-induced relaxation was significantly inhibited when the artery was treated with tetraethylammonium or SKF 525a. Results suggest that short term hypercholesterolemia modulates endothelium-derived hyperpolarizing factor-mediated relaxation in rabbit renal artery.View full abstractDownload PDF (129K)
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