The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 65 , Issue 1
Showing 1-14 articles out of 14 articles from the selected issue
  • Ichiro Hirotsu, Makoto Koyama, Naomi Honbo, Tomochika Ohno
    1994 Volume 65 Issue 1 Pages 1-7
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    (+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma ligand, at doses above 3 mg/kg (s.c.) increased the ambulatory activity of rats, while the (-) isomer of 3-PPP with low affinity for sigma receptors, did not significantly modify the ambulatory activity at 10 and 30 mg/kg (s.c.). The ambulation-increasing effect of (+)-3-PPP was prevented by the sigma receptor antagonists BMY 14802 and rimcazole or the sigma/dopamine D2 antagonist haloperidol. The (+)-3-PPP effect was also attenuated by pretreatment with the monoamine depletor reserpine or the tyrosine hydroxylase inhibitor α-methyltyrosine, but was not affected by the tryptophan hydroxylase inhibitor p-chlorophenylalanine. Moreover, the (+)-3-PPP effect was antagonized by the dopamine D2 antagonist sulpiride, whereas pretreatment with the 5-HT1A agonist 8-OH-DPAT and the a-adrenoceptor antagonist phenoxybenzamine did not exert any significant effect. These results indicate that sigma receptors are involved in the neuronal mechanism(s) of hyperambulation induced by (+)-3-PPP, and the sigma system may exert both a presynaptic action and a dopamine D2 receptor-mediated action to increase the central dopaminergic function.
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  • Hitoshi Matsukura, Makoto Masuda, Kazuhiko Kawaguchi, Aoi Uchida, Tosh ...
    1994 Volume 65 Issue 1 Pages 9-18
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The cytoprotective effect of NC-1300-O-3 and its mechanism of action were investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HCl-ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-3 and necrotizing agents in the stomach, which is considered to be related to the development of cytoprotection, was not observed. A preventive effect of NC-1300-O-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omeprazole. This suggests that the cytoprotective effect of NC-1300-O-3 is an action on the gastric mucosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-0-3 was not affected by pretreatment with indomethacin but was partly decreased by N-ethylmaleimide pretreatment, suggesting the participation of endogenous sulfhydryl compounds in the action of NC-1300-O-3. This compound dose-dependently increased the hexosamine content in the gastric lumen in rats at a dose range of 3-30 mg/kg, p.o. and slightly inhibited a reduction in surface mucus and mucosal hexosamine content caused by necrotizing agents. Moreover, NC-1300-O-3 at doses of 10 and 30 mg/kg, p.o. significantly inhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in potential difference caused by aspirin in rats. These actions were suggested to contribute to the cytoprotective effect of NC-1300-O-3.
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  • Katsumi Ishii, Ikuhisa Yakuo, Satoru Motoyoshi, Hiroyo Nakagawa, Hideo ...
    1994 Volume 65 Issue 1 Pages 19-25
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The effects of AL-3264, which exhibits a 5-lipoxygenase (5-LO) inhibiting property by blocking histamine H1-receptors and inhibition of histamine release, were examined on leukotriene (LT) production and LT-mediated responses. AL-3264 (1-30 μM) inhibited the A23, 187-induced LT production from human leukocytes with almost the same potency as that of nordihydroguaiaretic acid. AL-3264 (30-100 mg/kg, p.o.) inhibited the antigen-induced LT production in the abdominal cavity of passively sensitized rats; its effect was as potent as that of AA-861, a 5-LO inhibitor. AL-3264 (30 μM) suppressed both the initial and sustained phases of the antigen-induced contractions in isolated trachea from actively sensitized guinea pig. Phenidone (3 μM), a dual inhibitor of 5-LO and cyclooxygenase (CO), suppressed the sustained phase, while indomethacin was without effect on either phase. AL-3264 (40-160 mg/kg, p.o.) suppressed the arachidonic acid-induced ear edema in mice, for which 5-LO inhibitors were effective but antihistamines were not. The anti-edematous effect of AL-3264 (160 mg/kg) was reduced by intradermal administration of LTC4 (0.1 μg). These results suggest that AL-3264 suppresses LT production in vivo and in vitro by inhibiting 5-LO activity, and this property may contribute to the antiallergic effect of AL-3264.
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  • Angky Soekanto
    1994 Volume 65 Issue 1 Pages 27-34
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The present study examined the effect of sodium salicylate and indomethacin on the recruitment of osteoclast-like cells in vitro. When mouse bone marrow cells were cultured for 8 days with 1α, 25-dihydroxyvitamin D3 (1α, 25-(OH)2D3, 10-8 M), prostaglandin E2 (PGE2, 10-6 M) and recombinant human interleukin-1α (rHIL-1α, 2 ng/ml), numerous tartrate-resistant acid phosphatase (TRAP-positive) multinucleated cells (MNCs) formed. Adding sodium salicylate or indomethacin inhibited the formation of TRAP-positive MNCs in a dose-dependent manner. This inhibitory effect was more pronounced when the drugs were given at a later stage in the culture period. Indomethacin appeared to be more potent than sodium salicylate. PGE2 production was inhibited by sodium salicylate or indomethacin. Exogenous PGE2 failed to overcome the inhibitory effect of both drugs. These results suggest that sodium salicylate and indomethacin have inhibitory effects on the recruitment of osteoclast-like MNCs, preferentially on the later stage, and that PGE2 is not the only compound targeted by these drugs in reducing osteoclast-like cell formation in mouse bone marrow culture.
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  • Takashi Tomiuga, Masatoshi Kobayashi, Yoshikage Nakajima, Motoaki Bess ...
    1994 Volume 65 Issue 1 Pages 35-43
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The effects of menatetrenone (2-methyl-3-tetraprenyl-1, 4-naphthoquinone, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietary supplement. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK-4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.
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  • Hiroyuki Satoh, Toshiaki Kobayashi, Katsuya Higo, Akira Karasawa
    1994 Volume 65 Issue 1 Pages 45-50
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    We investigated the effect of KW-3635, a selective thromboxane (TX) A2-receptor antagonist, on the arachidonic acid (AA)-induced transient cerebral ischemia in anesthetized dogs. Intracarotid-arterial injection of AA (0.25-1 mg/kg) produced a transient and reversible decrease in electroencephalographic (EEG) activity. The reduction of EEG power was inhibited by the intravenous injection of KW-3635 or aspirin, a cyclooxygenase inhibitor. Local cortical perfusion (LCP) measured by a laser-doppler flow meter was also reduced concomitantly with the reduction of EEG power. Although KW-3635 at 1 and 3 mg/kg (i.v.) did not affect the maximum reduction of LCP, the duration of the reduction period of LCP was significantly shortened by KW-3635. On the other hand, aspirin at 1 and 3 mg/kg (i.v.) inhibited both the maximum and the delay of LCP reduction. The intravenous administration of KW-3635 or aspirin caused dose-dependent inhibition of ex vivo platelet aggregation stimulated by AA (150 μM) at the doses that improve the EEG activity. These data suggest that TXA2 is one of the important factors in the AA-induced transient reduction of EEG activity in anesthetized dogs. The TXA2-receptor antagonist may be useful for protection against the ischemic brain damage following transient ischemic attack.
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  • Jun Matsumoto, Toshie Takahashi, Mitsuji Agata, Hatsunori Toyofuku, Na ...
    1994 Volume 65 Issue 1 Pages 51-57
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    3-[4-[3-(1H-Imidazol-1-yl)propoxy]phenyl]-5-trifluoromethyl-1, 2, 4-oxadiazole (IFO), design ed to be a novel selective inhibitor of monoamine oxidase (MAO), showed highly selective inhibition for type-B (MAO-B); its IC50 was approximately > 200 μM and 30 nM for type-A (MAO-A) and MAO-B, respectively, in the standard assay using mitochondrial preparations from rat brain or liver. The in vitro MAO-B inhibition by IFO was time-independent, non-competitive and tight-binding; and furthermore, in the presence of sodium cholate its inhibition was not tight-binding and was reversible. Oral administration of IFO (0.5-100 mg/kg) produced a dose-dependent MAO-B inhibition in mouse brain; its ED50 (p.o., 1 hr) was 1.6 mg/kg, while L-deprenyl inhibited the enzyme with the ED50 of approximately 8.0 mg/kg. The ED50 for MAO-A was > 100 mg/kg for either IFO and L-deprenyl. The MAO inhibitive effect of IFO in mouse liver was the same as that in the brain, but that of L-deprenyl in mouse liver was different from that in the brain as shown by the ED50 values of 35 mg/kg and 0.6 mg/kg for MAO-A and MAO-B, respectively. In mice, IFO increased the striatal concentrations of 2-phenylethylamine (2-PEA) and showed almost the same protective efficacy as L-deprenyl against the lethality and striatal dopamine (DA) depletion induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). These results indicate that IFO appears to be a potent inhibitor of MAO-B in mouse brain.
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  • Toru Kawanishi, Megumi Kawanishi, Hisayuki Ohata, Kazuhiro Toyoda, Mic ...
    1994 Volume 65 Issue 1 Pages 59-62
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The relationship between spontaneous Ca2+ oscillations and cell proliferation was investigated in cultured longitudinal muscle cells from guinea pig ileum. BAPTA, caffeine, thapsigargine and La3+ suppressed the spontaneous Ca2+ oscillations and the DNA synthesis at 5.0 mM, 10.0 mM, 15.62 nM and 0.5 mM, respectively, whereas verapamil, nicardipine and ryanodine did not suppress either. However, BAPTA and La3+ did not inhibit the DNA synthesis at 1.25 mM and 0.13 mM, but did suppress the Ca2+ oscillations even at 1.0 mM and 0.1 mM, respectively. These results show that the spontaneous Ca2+ oscillations are not prerequisite for the cell proliferation.
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  • Takafumi Ichikawa, Kazuhiko Ishihara, Yumi Ogata, Susumu Ohara, Katsun ...
    1994 Volume 65 Issue 1 Pages 63-66
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    We examined the effects of Z-300 (N-[3-[3-(piperidinomethyl)phenoxy]propyl]-2-(2-hydroxy-ethyl-1-thio)acetamido·2-(4-hydroxy benzoyl)benzoate), a newly-synthesized selective histamine H2-receptor antagonist, on mucin in rat gastric mucosa. Deep corpus mucin content increased significantly to 127% of the control after the administration of 30 mg/kg of Z-300, whereas that in the antral mucosa did not in crease. The addition of Z-300 significantly increased [3H]-labeled mucin in the corpus region. In the antrum, biosynthetic activity showed no significant change by 10-8-10-5M of Z-300. These results suggest that Z-300 not only inhibits acid secretion but may also promote gastric mucus metabolism in the corpus region.
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  • Kotaro Takasaki, Nobuyuki Kishibayashi, Akio Ishii, Akira Karasawa
    1994 Volume 65 Issue 1 Pages 67-71
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The effects of KW-5092, {1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene}propanedinitrile fumarate, on the loperamide or clonidine-induced delayed propulsion were determined in rats and compared with those of other gastroprokinetic agents. Administration of loperamide (0.3 mg/kg, s.c.) or clonidine (0.01 mg/kg, s.c.) induced delay of the evacuation time of the teflon ball, which had been inserted into the distal colon. The delayed evacuation was improved dose-dependently by KW-5092 at 3 to 10 mg/kg (p.o.) or higher. Neostigmine at 0.3 to 3 mg/kg (p.o.) and T-1815 at 1 to 100 mg/kg (p.o.) also improved the delayed ball evacuation. These results suggest that KW-5092 stimulates the delayed colonic propulsion.
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  • Yoshiko Uchiyama, Katsuya Morita, Shigeo Kitayama, Tetsuo Suemitsu, Na ...
    1994 Volume 65 Issue 1 Pages 73-77
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    The role of nitric oxide (NO) in neurotransmitter release was studied using bovine adrenal medullary chromaffin cells. L-Arginine and sodium nitroprusside (SNP) slightly increased the intracellular free calcium concentration ([Ca2+]i), and the effects of the agents were dependent on the presence of the extracellular Ca2+ ([Ca2+]o), but were not blocked by verapamil (30 μM) or diltiazem (30 μM). SNP enhanced the acetylcholine (ACh)-induced rise in [Ca2+]i in the presence but not in the absence of [Ca2+]o. The effects of L-arginine but not those of SNP were inhibited by Nω-nitro-L-arginine (L-NNA). L-NNA significantly reduced the ACh-induced rise in [Ca2+]i and catecholamine (CA) release, and the reduction was restored by L-arginine but not by D-arginine. These results suggest a possible involvement of NO in ACh-induced [Ca2+]i rise and CA release in bovine adrenal chromaffin cells.
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  • Masataka Majima, Yoshikazu Kuribayashi, Yasuhiro Ikeda, Keiichi Adachi ...
    1994 Volume 65 Issue 1 Pages 79-82
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    Ebelactone B (EB) (10-7-10-5 M) inhibited dose-dependently carboxypeptidase (CP) Y-like exopeptidase, one of the major kininases separated from rat urine, whereas it inhibited neither CPA, CPB or neutral endopeptidase (NEP). Degradation of bradykinin (BK) to BK-(1-8) in rat urine was completely inhibited by EB (10-5 M) with the increased generation of BK-(1-7). Intraduodenal administration of EB (3 mg/kg) to anesthetized rats caused marked diuresis (by 110%) and natriuresis (130%), in parallel with the increase in urinary kinin levels (110%). Intravenous infusion of a BK antagonist, Hoe140 (3 mg/kg/hr), strongly blocked both EB-induced diuresis and natriuresis. EB may be a novel type of diuretic and natriuretic agent that acts by increasing urinary kinin levels.
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  • Kwok-Hung Sit, Ramanujam Paramanantham, Boon-Huat Bay, Kim-Ping Wong
    1994 Volume 65 Issue 1 Pages 83-87
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    Flow cytometric cell-by-cell evaluation of NH4Cl acidification of human Chang cells showed that at steady state, 3% of the cells remained alkalinized (>pHi 7) over an extended period (up to 80 min) despite the absence of extracellular Na+ and HCO3-. In fluorescence microscopy, the acidification-resistant cells were characteristically rounded M-phase cells. Both mean cytosolic pH and M-phase alkalinity were however sensitive to (a) azide and oligomycin, inhibitors of F-ATPase (ATP synthase), and to (b) vanadium ions, the phosphate analogue of P-ATPase (ATP-hydrolyzing), in dose-dependent and time-dependent man ners. Dead cell indices were constant at ≈ 10%. Thiocyanate chaotrophic anions, which cleave the V-ATPase structure, had no effect. Since ATP synthesizing F-ATPase (ATP synthase) is coupled to ATP-hydrolyzing P-ATPase as ''master-&-slave'', azide- and oligomycin-sensitivity corroborated with vanadate-sensitivity in suggesting energized proton pumping modulating (a) M-phase alkalinity and (b) cytosolic pH, against acidification.
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  • Shin-ichi Ide, Mari Kondoh, Hiroyuki Satoh, Akira Karasawa
    1994 Volume 65 Issue 1 Pages 89-92
    Published: 1994
    Released: April 10, 2006
    JOURNALS FREE ACCESS
    We examined the effect of benidipine, a long lasting Ca2- channel blocker, on balloon catheterization-induced intimal thickening of the carotid artery in rats. In the carotid arteries of vehicle-treated rats, neo-intima formation and elevation of DNA content was observed at 14 days after the surgery. Benidipine (5 mg/kg, p.o., b.i.d.) halved the intimal thickening and suppressed the elevated DNA-content in the balloon catheter-injured artery. These results suggest that benidipine may be useful for the treatment of vascular proliferative diseases like restenosis following percutaneous transluminal angioplasty.
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