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Volume 65 (1994)
- Issue 4 Pages 297-
- Issue 3 Pages 179-
- Issue 2 Pages 93-
- Issue 1 Pages 1-
Volume 65, Issue 4
Displaying 1-11 of 11 articles from this issue
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Katsumi Ishii, Satoru Motoyoshi, Joe Kawata, Hiroyo Nakagawa, Kunihiko ...1994 Volume 65 Issue 4 Pages 297-303
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSThis study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E2 (PGE2, 1 μg/ear), but not by concomitant intradermal application of leukotriene C4 (LTC4, 0.1 μg/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC4, but not by PGE2. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB4 13-15 times more potently than that of PGE2 in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC4, but not by PGE2. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC4 or PGE2 with AA is a useful method for differential evaluation of these inhibitors.View full abstractDownload PDF (457K) -
Nobuo Kosaka, Hiroshi Tanaka, Atsushi Tomaru, Akio Ishii, Katsuichi Sh ...1994 Volume 65 Issue 4 Pages 305-312
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSEffects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 =1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50=4.5-39.8 mg/kg, p.o.). In addition, the cytoprotecive effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.View full abstractDownload PDF (481K) -
A.F.M. Mohibur Rahman, Masakatsu Takahashi, Hiroshi Kaneto1994 Volume 65 Issue 4 Pages 313-317
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSABSTRACT-The mechanism underlying the previous findings that the development of antinociceptive tolerance to morphine was significantly delayed in the presence of inflammatory pain induced by formalin was examined. Measurements of the pain threshold at different time intervals have shown that pain lasts around one week in the formalin treated mice. A single dose of indomethacin (10 mg/kg) or aspirin (400 mg/kg), 30 min before formalin injection, and daily 400 mg/kg of aspirin had no effects on the pain threshold or swelling, and it also did not affect the delay of morphine tolerance development. Daily administration of diazepam, 1 mg/kg, 1 hr before morphine injection completely abolished the delay. This effect was antagonized by 2 mg/kg of flumazenil, administered 15 min before diazepam injection. These results suggest that pain-associated anxiety participates in the delay of morphine tolerance development and consequently the benzodiazepine-receptor complex plays a role in the development of morphine tolerance during a painful state.View full abstractDownload PDF (344K) -
Hitoshi Matsukura, Makoto Masuda, Aoi Uchida, Toshiro Kamishiro1994 Volume 65 Issue 4 Pages 319-326
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSWe investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC-1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreat ment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300-O-3.View full abstractDownload PDF (559K) -
Yuichi Hattori, Satoshi Gando, Masato Nagashima, Morio Kanno1994 Volume 65 Issue 4 Pages 327-336
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSThe difference in histamine receptor subtypes that are involved in the positive inotropic effect of histamine in guinea pig and rabbit ventricular myocardium was analytically characterized. In guinea pig papillary muscles, the positive inotropic effect of histamine was antagonized by cimetidine but not by mepyramine. The converse was true in rabbit papillary muscles. However, histamine evoked a positive inotropic effect through H1- and H2-receptors after blockade of H2- and H1-receptors in guinea pig and rabbit papillary muscles, respectively. Adenylate cyclase was significantly activated by histamine via H2-receptors in guinea pig but not in rabbit myocardial ventricular membranes. Accumulation of [3H]inositol monophosphate in ventricular strips prelabeled with myo-[3H]inositol was increased by histamine via H1-receptors to a similar extent in rabbits and guinea pigs. Radioligand binding experiments with [3H]mepyramine and [3H]tiotidine showed an increased number of H1-receptors and a decreased number of H2-receptors in guinea pig compared with rabbit ventricular myocardium. These results suggest that the positive inotropic effects of histamine are dominated by an H1-receptor-mediated effect in rabbits and by an H2-receptor-mediated one in guinea pig ventricular myocardium, and the positive inotropic effect manifested by one subtype apparently restricts the expression of the positive inotropic effect mediated by the other subtype. This species difference is not due to a difference in densities of the receptor subtypes, but may be partly related to a difference in the extents of coupling of H2-receptors to adenylate cyclase.View full abstractDownload PDF (787K) -
Takeshi Suzuki, Hikaru Nonaka, Kazuko Fujimoto, Koichiro Kawashima1994 Volume 65 Issue 4 Pages 337-342
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSWe examined the effects of tacrine (9-amino-1, 2, 3, 4-tetrahydroacridine) on endogenous acetylcholine (ACh) release from rat hippocampal slices. Tacrine (more than 1 μM) increased the measurable amount of basal ACh release. On the other hand, in the presence of physostigmine (50 μM; under this condition, cholinesterase activity was inhibited), tacrine did not enhance the basal ACh release. Tacrine at more than 100 μM increased the submaximal electrical stimulation-evoked release of ACh in both the absence and presence of physostigmine (50 μM). This effect of tacrine was abolished by a combination of atropine (100 nM) and physostigmine. These results indicate that a high-dose of tacrine increases cholinergic neurotransmission not only by inhibition of cholinesterase but also by increasing ACh release through an atropine-like effect, perhaps by blockade of part of the process of muscarinic autoinhibition.View full abstractDownload PDF (349K) -
Naoyuki Tsutsumi, Kohtaro Kawashima, Hideo Nagata, Junko Tsuyuki, Fumi ...1994 Volume 65 Issue 4 Pages 343-349
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSWe previously found that 3, 9-bis(N, N-dimethylcarbamoyloxy)-5H-benzofuro[3, 2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1α, 25-dihydroxyvitamin D3- and interleukin 1β-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is as effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.View full abstractDownload PDF (479K) -
Kazuhide Yoshida, Tomio Okamura, Noboru Toda1994 Volume 65 Issue 4 Pages 351-359
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSNitroxidergic nerves and their functional role were determined in a variety of monkey arteries. Nitric oxide synthase-immunoreactive nerve fibers innervating the monkey arterial wall were histochemically determined by the use of nitric oxide synthase antiserum. Thin nitric oxide synthase-immunoreactive fibers were consistently found in the outer media of monkey cerebral, mesenteric and temporal arteries, in addition to many thicker fibers and nerve bundles in the adventitia. In the monkey pterygopalatine ganglion, the immunoreactivity was clearly seen in nerve cells, bundles and fibers. Helical strips of monkey arteries were exposed to the bathing media for tension recordings and were stimulated by electrical square pulses. In helical strips of the cerebral artery denuded of the endothelium, transmural electrical stimulation produced relaxations that were abolished by tetrodotoxin or NG-nitro-L-arginine, a nitric oxide synthase inhibitor. In the monkey mesenteric and temporal arterial strips treated with α-adrenoceptor antagonists, the relaxation caused by electrical stimulation was also abolished by the nitric oxide synthase inhibitor, and it was restored by L-arginine. Nitroxidergic perivascular nerves, histologically demonstrated, appear to play an important role in dilating the monkey cerebral artery and in counteracting a vasoconstriction associated with noradrenergic nerve activation in the mesenteric and temporal arteries.View full abstractDownload PDF (690K) -
Atsushi Tomaru, Akio Ishii, Nobuyuki Kishibayashi, Akira Karasawa1994 Volume 65 Issue 4 Pages 361-365
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSThe present study examined whether adenosine agonists influence the occurrence of giant migrating contractions (GMCs) induced by glycerol enema (65%, 2 ml/kg) in rats. Catheter pressure transducers were used to measure the colonic luminal manometric alterations. The adenosine A1 agonists (2S)-N6-(2-endo-norbornyl)adenosine ((S)-ENBA) (10 μg/kg, i.v.) and N6-cyclohexyladenosine (30 μg/kg, i.v.) abolished the GMCs, whereas the adenosine A2 agonist 2-[p-(2-carboxyethyl)phenethylamino]-5''-N-ethylcarboxamidoadenosine (CGS 21680) (30-300 pg/kg, i.v.) failed to influence the GMCs. The suppressive action of (S)-ENBA on the GMCs was entirely counteracted by the peripheral adenosine antagonist 8-(p-sulfophenyl)theophylline (10 mg/kg, i.v.). The present observations suggest that the adenosine A1 agonist suppresses the GMCs via peripheral adenosine receptors.View full abstractDownload PDF (291K) -
Toshio Kumai, Masami Tanaka, Minoru Watanabe, Shinichi Kobayashi1994 Volume 65 Issue 4 Pages 367-369
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSWe investigated the expression of tyrosine hydroxylase (TH) mRNA and its activity in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern blot and dot blot analyses. The TH activity and the expression of TH mRNA in the adrenal medulla of SHR were significantly higher than those of WKY (P <0.01). These results suggested that the hypertension of SHR may be related to the high activity of TH due to the high level of TH mRNA, which increases epinephrine and norepinephrine levels in the adrenal medulla.View full abstractDownload PDF (221K) -
Masato Tamura, Susumu Kagawa, Yoshihiro Tsuruo, Kazunori Ishimura, Kyo ...1994 Volume 65 Issue 4 Pages 371-373
Published: 1994
Released on J-STAGE: April 10, 2006
JOURNAL FREE ACCESSThe effects of flavonoids on NADPH diaphorase activity were studied in vitro, and we found that the enzyme activity was markedly inhibited by quercetin. This inhibitory action was shown to be accompanied by an increase in the apparent Km value of the enzyme for the cofactor NADPH, with a decrease in the Vmax, and an increase in the apparent Km for the substrate nitro blue tetrazolium, without any significant change in the Vmax. These results indicate that quercetin may directly inhibit NADPH diaphorase, thus suggesting the possibility that this compound may be able to inhibit the production of nitric oxide in the brain.View full abstractDownload PDF (216K)
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