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Volume 73 (1997)
- Issue 4 Pages 263-
- Issue 3 Pages 185-
- Issue 2 Pages 105-
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Volume 73, Issue 4
Displaying 1-14 of 14 articles from this issue
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Yasushi Ohizumi1997 Volume 73 Issue 4 Pages 263-289
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSNumerous neurotoxins that alter Na+-channel function have been shown to be useful tools for characterizing Na+ channels. Polypeptide blockers of voltage-dependent K+ channels (dendrotoxins, etc.) and Ca2+ -activated K+ channels (apamine, etc.) have been studied extensively by numerous investigators. Peptide toxins, calciseptine and ω-conotoxins have been attracting much attention as inhibitors of L-type and N-type Ca2+ channels, respectively, while ω-conotoxins-MVIIC and ω-agatoxin IVA have been used as new types of Ca2+ -channel blockers. Ryanodine and bromoeudistomin D analogues have been extensively used to elucidate Ca2+ -release-channel functions and to purify its target protein. Polypeptide toxins (myotoxin α, etc.) and macrolides (FK 506, etc.) are useful Ca2+ releasers with a novel mechanism, while natural products such as thapsigargin and gingerol have been used as modulators of Ca2+ -pumping ATPase. Some modulators of the function of myosin (purealin, etc.) and actin (goniodomin A, etc.)have been demonstrated to be important chemical probes for understanding the physiological roles of the contractile proteins in structural changes and their interaction in muscle contraction. A large number of protein kinase inhibitors (staurosporine, etc.) and phosphatase inhibitors (okadaic acid, etc.)are widely used as first-choice reagents for studying protein phosphorylation. These natural products have become essential tools for studying the regulatory mechanism of cellular ion movements, muscle contraction and protein phosphorylation.View full abstractDownload PDF (1895K) -
Masato Kakiuchi, Tetsuo Ohashi, Keiichi Musoh, Kimio Kawamura, Kouji M ...1997 Volume 73 Issue 4 Pages 291-298
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5, 11-dihydrobenz[b]oxepino[4, 3-b]pyridin-11-ylidene)-piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent, on the central nervous system (CNS). Its selectivity for the histamine H1-receptor and its ability to penetrate into the CNS were compared with those of typical antiallergic agents and the nonamphoteric basic compound PY-608 (8-fluoro-5, 11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxepino[4, 3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1-receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the H1receptor was low. The inhibitory effects of these antiallergic agents on histamine-induced increase of vascular permeability in mice (ED50)were compared with the displacement of [3H]mepyramine binding to H1receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1-receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H1-receptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.View full abstractDownload PDF (571K) -
Hiroshi Satoh, Fumihiko Sato, Kenji Takami, Sandor Szabo1997 Volume 73 Issue 4 Pages 299-309
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 μl of 3% N-ethylmaleimide (NEM)or iodoacetamide (IA)was introduced into the colon via a Nelaton''s catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1 3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.View full abstractDownload PDF (885K) -
Takehiro Yamada, Toshihiko Murayama, Yasuyuki Nomura1997 Volume 73 Issue 4 Pages 311-316
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSSeveral studies have shown that the nervous (and hormonal)system controls immune functions. In the present study, we examined the presence of muscarinic acetylcholine receptors and the effect of carbachol on DNA fragmentation in adult rat thymocytes. Rat thymocytes possessed high affinity binding sites for the muscarinic antagonist [3H]3-quinuclidinyl benzilate (QNB). The average number of binding sites per cells was 3000, and the equilibrium dissociation constant of [3H]QNB on intact cell was approximately 80 nM. The binding was inhibited by an Ml and M3-selective antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodine (4-DAMP). Hydrocortisone (100 mg/kg, s.c.)treatment of rats for 2 days prior to sacrifice increased the average number of [3H]QNB binding sites on thymocytes by 82±33%. The gel electrophoresis of DNA extracted from carbachol-treated thymocytes revealed a ladder pattern typical of intranucleosomal fragmentation. The addition of oxotremorine-M also induced DNA fragmentation and the effects of muscarinic agonists were inhibited by the addition of atropine or 4-DAMP. The results suggest the existence of muscarinic receptors and the possible involvement in apoptosis in thymocytes.View full abstractDownload PDF (385K) -
Hiroshi Kawazura, Yasuhiro Takahashi, Yoshio Shiga, Fumiki Shimada, No ...1997 Volume 73 Issue 4 Pages 317-324
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSMS-153 ((R)-(−)-5-methyl-l-nicotinoyl-2-pyrazoline)is a novel pyrazoline compound that has potent cerebroprotective effects in the rat focal cerebral ischemia model. Middle cerebral artery (MCA)occlusion in rats allows detailed assessment of both functional and morphological sequelae of brain infarct. Using this model, we evaluated the cerebroprotective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 7 days)significantly reduced infarct volumes and improved neurological deficits in MCA occluded rats 7 days after occlusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 21 hr)administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr)administration was started 6 hr after occlusion.View full abstractDownload PDF (537K) -
Yoji Sato, Hitoshi Kurose, Taku Nagao1997 Volume 73 Issue 4 Pages 325-332
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSTo examine the contribution of β-adrenoceptor (βAR) downregulation to desensitization of βARs by chronic administration of a βAR agonist, we compared the adenylyl cyclase (AC) activities in two kinds of cardiac ventricular membranes with decreased available βARs: one was derived from rats infused with a selective β1AR agonist, T-0509 [(−)-(R)-1-(3, 4-dihydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl)amino]ethanol hydrochloride], in vivo (40 μg/kg/hr, s.c. for 6 days); and the other was obtained from treatment of control membranes with an irreversible βAR antagonist, bromoacetyl alprenolol methane (BAAM). T-0509 infusion decreased the densities of β1ARs and, β2ARs by 26% and 32%, respectively, and reduced the maximal isoproterenol-stimulated AC activity by 53%. The amount of Gsα and Giα proteins in the membranes was not significantly changed by T-0509 infusion. To make preparations that mimic the T0509-induced downregulation, we treated the control membranes with 100 nM BAAM in vitro. The BAAM treatment decreased the Bmax, value of [125I] iodocyanopindolol for β1ARs and β2ARs by 29070 and 36070, respectively, whereas it reduced the maximal effect of isoproterenol on AC activity only by 37%. These results suggest that downregulation of βARs cannot fully account for the desensitization by chronic treatment of T-0509 and that other mechanism(s) can play a significant role in the loss of responsiveness.View full abstractDownload PDF (621K) -
Yoshinari Matsumoto, Masashi Kato, Yasuhiko Tamada, Hijiri Mori, Masar ...1997 Volume 73 Issue 4 Pages 333-336
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated the effects of Sho-saiko-to, the most commonly used herbal medicine in Japan, on the production of interleukin (IL)-la by cultured human epidermal keratinocytes. IL-lα production was significantly promoted by treatment with 100 or 500 μg/ml Sho-saiko-to for 24 or 48 hr. Expression of IL-lα receptors was the most markedly upregulated after treatment with 500 μg/ml Sho-saiko-to for 24 hr and with 100 or 500 μg/ml for 48 hr; these cells showed the characteristics of multilayered differentiated keratinocytes. The presence of an anti-IL-lα antibody during the treatment with 500 μg/ml of Sho-saiko-to for 24 or 48 hr or with 100 μg/ml for 48 hr significantly down-regulated the synthesis by the keratinocytes and induced damages in them. Keratinocytes treated with Sho-saiko-to might produce IL-lα and express IL-lα receptors. IL-lα may regulate the proliferation and differentiation of keratinocytes after Sho-saiko-to treatment. These findings suggest that Sho-saiko-to enhances the autocrine growth mediated by IL-lα.View full abstractDownload PDF (278K) -
Toshihiro Shinosaki, Ikuko Takagawa, Norio Sunagawa, Yukio Yonetani, H ...1997 Volume 73 Issue 4 Pages 337-345
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe therapeutic effects of angiotensin converting enzyme inhibitor, lisinopril, on puromycin aminonucleoside (PAN)-induced nephrosis were investigated using unilaterally nephrectomized rats. Lisinopril showed potent dual effects on PAN nephrosis. Lisinopril treatment (50 mg/l in drinking water)from day 5 or day 9 reduced urinary protein excretion and suppressed the development of glomerular sclerosis at 8 weeks after PAN injection (150 mg/kg, i.p.), indicating a therapeutic effect on the nephrosis. Recovery of decreased anionic charge sites on the glomerular basement membrane was involved, at least in part, in the therapeutic action of lisinopril against proteinuria. On the other hand, oliguria and progressive azotemia derived from continuous deterioration of the renal function was induced if the treatment of lisinopril was started on the same day as PAN injection. The renal dysfunction induced by simultaneous administration of lisinopril with PAN could be abolished by combination dosing with sarcosine, an angiotensin II (AII)-receptor agonist. These results indicate that lisinopril treatment attenuates proteinuria by ameliorating the anionic charge barrier on the glomerular basement membrane and that it also protects against the development of chronic renal disease with segmental glomerular sclerosis, although All depletion during the acute nephrotic stage exacerbates the renal damage in PAN nephrosis of unilaterally nephrectomized rats.View full abstractDownload PDF (1153K) -
Takatoshi Tanabe, Hitomi Otani, Katsuyuki Mishima, Ryokei Ogawa, Chiyo ...1997 Volume 73 Issue 4 Pages 347-351
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe successfully detected the oxyradical production in human synovial A (macrophage-like)and B (fibroblast-like)cells by phorbol 12-myristate 13-acetate (PMA)using the luminol-chemiluminescence method. The PMA (0.1 μg/ml)-induced photon generation was abolished by an O2- scavenger, superoxide dismutase, and an H202 scavenger, catalase, suggesting that the stimulus produced oxyradicals in synovial cells. Both of these responses were abolished by a protein kinase C (PKC)inhibitor, calphostine C, but unaffected by an intracellular Ca2+ chelator, BAPTA-AM, and Ca2+ removal from the extracellular medium. These findings suggest that synovial A and B cells produce oxyradicals through PKC-mediated and [Ca2+]i-independent mechanisms, probably through the activation of NADPH oxidase.View full abstractDownload PDF (471K) -
Kinzo Matsumoto, Shin-ichi Kohno, Yasuhiro Tezuka, Shigetoshi Kadota, ...1997 Volume 73 Issue 4 Pages 353-356
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated the effect of the aqueous extract of Japanese angelica root (JAR)on pentobarbital (PB)sleep in group-housed and socially isolated mice. The JAR extract (1.25-2.5 g/kg, p.o.)dose-dependently reversed the decrease in PB sleep caused by isolation stress without affecting PB sleep in group-housed mice. The JAR extract (2.5 g/kg, p.o.)also antagonized the decrease in PB sleep caused by the α2-adrenoceptor antagonists yohimbine and idazoxan (1 mg/kg, i.p.)and the α1-adrenoceptor agonist methoxamine (200 nmol, i.c.v.)in group-housed mice. These results suggest that the JAR extract reverses changes in the arousal level caused by isolation stress and the activation of central noradrenergic systems.View full abstractDownload PDF (322K) -
Ken-ichi Katayama, Kiyoshi Asano, Keiichiro Haga, Takemi Fukuda1997 Volume 73 Issue 4 Pages 357-360
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe binding affinity of azasetron hydrochloride (azasetron)for the 5-hydroxytryptamine3 (5-HT3)receptor in a tissue preparation of rat small intestine was investigated by using [3H]granisetron as a radioligand. Scatchard analysis of specific [3H]granisetron binding revealed a single population of saturable binding sites in the tissue preparation. At this site, azasetron was concentration-dependently competitive with [3H]granisetron, and it inhibited the specific [3H]granisetron binding with a Ki value of 0.33 nM. Azasetron has a high affinity for 5-HT3 receptor in the gastrointestinal organ, the very site of its antiemetic action against chemotherapy-induced emesis.View full abstractDownload PDF (246K) -
Masami Tanaka, Sachiko Nakaya, Minoru Watanabe, Toshio Kumai, Tomonori ...1997 Volume 73 Issue 4 Pages 361-363
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated the possibility that physiological doses of estrogen protect against atherosclerotic change produced by changes in vascular angiotensin-converting enzyme (ACE)activity. Rats were ovariectomized, and after 14 days, treated with estradiol-17β(0.2 μg/rat)for 14 weeks. Aorta ACE activity significantly increased in the ovariectomized rats, and decreased following estradiol-17β administration to a level not different from proestrous control rats. These results suggest that the lack of estrogenic action increases atherosclerotic change associated with changes in aorta ACE activity and that estrogen replacement therapy reduces the risk of atherosclerotic change associated with the decrease of aorta ACE activity.View full abstractDownload PDF (240K) -
A.N. Ehsanul Hoque, Nina Hoque, Akiyoshi Hara, Hiroko Hashizume, Kazuo ...1997 Volume 73 Issue 4 Pages 365-369
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSGlobal ischemia (15 min)followed by reperfusion (10, 20 or 30 min)was performed in isolated, working rat hearts. Ischemia depressed mechanical function, which was not restored by reperfusion of 20 min. Preischemic administration of K-7259 (N, N''-bis[4-(3, 4, 5-trimethoxyphenyl)butyl]homopiperazine dihydrochloride)(1, 5 or 10 μM)decreased the function before ischemia, but it attenuated the ischemia-induced dysfunction during reperfusion (20 min). Postischemic administration of K-7259 (10 μM)or dilazep (20 μM)also attenuated the ischemia-induced dysfunction during reperfusion (30 min). Ischemia-reperfusion (10 min)increased the tissue malondialdehyde level, and postischemic administration of K-7259 (10 μM)or dilazep (20 μM)attenuated the malondialdehyde accumulation. K-7259 has a cardioprotective effect when given either before or after ischemia.View full abstractDownload PDF (359K) -
Toshiaki Kume, Hanae Kohchiyama, Hiroyuki Nishikawa, Takehiko Maeda, S ...1997 Volume 73 Issue 4 Pages 371-374
Published: 1997
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe effects of an ether extract of fetal calf serum (EE-FCS)on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. The simultaneous addition of EE-FCS and glutamate reduced glutamate cytotoxicity in a concentration-dependent manner. EE-FCS also reduced the cytotoxicity induced by S-nitrosocysteine, a nitric oxide (NO)donor. The findings indicate that EE-FCS contains lipid-soluble, non-peptide substances with neuroprotective actions against NO-mediated glutamate neurotoxicity.View full abstractDownload PDF (213K)
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