H Kitagawa

Chiba University, Tiba, Chiba, Japan

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Publications (179)209.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of cytochrome P450 (P450) in lipid peroxidation induced by NADPH or peroxide was investigated in a reconstituted system. When cumene hydroperoxide, t-butyl hydroperoxide and hydrogen peroxide were used as initiators, the rates of malondialdehyde (MDA) formation were much higher in a reconstituted system containing P450 1A1 than those observed in a reconstituted system containing P450 1A2. In contrast to peroxide-induced lipid peroxidation, P450 1A2 catalysed NADPH-induced lipid peroxidation more effectively than did P450 1A1 regardless of the presence of ADP-Fe(NO3)3. Carbon monoxide inhibited NADPH-induced formation of MDA in a reconstituted system containing P450 1A2, but not P450 1A1. In addition, superoxide dismutase (SOD) was an effective inhibitor in a NADPH-induced lipid peroxidation system catalysed by P450 1A2 but not by P450 1A1. These results suggest that a peroxide-induced reaction might proceed readily with P450 1A1, whereas P450 1A2 mainly functions in NADPH-induced lipid peroxidation via generation of an active oxygen species. It is furthermore indicated that the difference in the effect of SOD in NADPH-induced lipid peroxidation depends on the P450 used.
    No preview · Article · Aug 1993 · Biochemical Pharmacology
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    ABSTRACT: General pharmacological properties of nebracetam were examined in various experimental animals and following results were obtained. 1) Nebracetam, only at 100 mg/kg (p.o.), showed depression of reactivity, potentiation of pentetrazol-induced convulsion and analgesic effect in mice, and fell body temperature in rats. 2) No remarkable difference was observed concerning the effect of nebracetam (racemate) and its optical isomer ((+) and (-)) on mouse general behavior. Whereas, WEB 2124 and WEB 1868, metabolite and decomposition of nebracetam did not influence on mouse general behavior up to 1000 mg/kg (p.o.). 3) Nebracetam did not show remarkable influence on various agonist-induced contraction of isolated guinea pig ileum. 4) Nebracetam induced mydriasis dose-dependently in rats (ED200 = 110.2 mg/kg p.o.). 5) Intravenous administration of nebracetam at 3 mg/kg or more increased heart rate and blood pressure. On the other hand, this agent did not affect carotid sinus reflex up to 100 mg/kg (i.v.) in rabbit. 6) Nebracetam up to 1000 mg/kg (p.o.) did not affect mouse intestinal transport. 7) Nebracetam did not affect urine volume, but this agent significantly increased electrolytes (Na+, K+, Cl-) excretion at 1000 mg/kg (p.o.). These results suggest that nebracetam shows the effect on general pharmacological properties only at high dose or high concentration, except mydriatic action in rats. Therefore, it is assumed that this agent is devoid of important side effect at clinical dose.
    No preview · Article · Jan 1992
  • I. Tsunenari · H. Nishiwaki · M. Izumita · H. Kitagawa · H. Kohei
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    ABSTRACT: α-blocking activity of epinastine were examined in the nasal mucosal blood flow of rabbit and isolated rat and guinea-pig blood vessel. Epinastine showed an α-blocking action in vivo and in vitro. However, this activity is weaker than that of phentolamine in the nasal mucosal blood flow of rabbits. Antihistaminic activity of epinastine was about 19 times more potent than α-blocking activity in isolated guinea-pigs aorta. It is assumed that epinastine has only weak α-blocking action, and does not any effect on the hemodynamics in the nasal mucosa.
    No preview · Article · Jan 1992
  • K Ueno · A R Saha · T Satoh · H Kitagawa
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    ABSTRACT: Heptaminol AMP amidate (HAA), a nucleotide derivative increased the percentage of T cell surface phenotypes on peripheral blood lymphocytes (PBL) of mice primed with sheep red blood cells. The T cell surface phenotypes Thy1.2, Lyt1, L3T4 and Lyt2 increased on the PBL of HAA administered mice to 136, 145, 144 and 153%, respectively over those on the PBL of control mice.
    No preview · Article · Feb 1991 · Research communications in chemical pathology and pharmacology
  • H Kitagawa · F Takeda · H Kohei
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    ABSTRACT: Effect of HCl on the endothelium-dependent increase in mucosal blood flow and effect of endothelium-derived relaxing factor (EDRF) inhibitors or nitrites on the HCl-induced gastric lesion were studied to clarify the effect of EDRF on the formation of gastric lesion in rats. Topical application of 0.6 N HCl on the gastric mucosa inhibited the endothelium-dependent increase in mucosal hemodynamics estimated using organ-reflectance spectrophotometry induced by vagal stimulation or acetylcholine, but not by papaverine. Collagenase, gossypol, hemoglobin and ascorbic acid have been reported to inhibit the endothelium-dependent vasodilation, inhibited increase in mucosal hemodynamics induced by vagal stimulation and acetylcholine. These inhibitors and methylene blue significantly enhanced the gastric lesion induced by 0.45 N HCl. Intra-arterial or topical application of nitrites (sodium nitrite and isoamyl nitrite) increased mucosal hemodynamics. Oral administration of nitrites prevented the formation of 0.6 N HCl-induced gastric lesion. These results suggest that EDRF plays an important role in the protection of gastric mucosa against HCl. Reduced endothelium-dependent increase in mucosal blood flow may be an etiology of gastric lesion in rats.
    No preview · Article · Jul 1990 · Journal of Pharmacology and Experimental Therapeutics
  • A R Saha · K Ueno · H Kitagawa · T Satoh
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    ABSTRACT: Hepataminol AMP amidate (HAA), a nucleotide derivative possessing immunopotentiating activities, inhibited the mitogen-induced proliferation of murine splenocytes in vitro at the higher concentrations. Concanavalin A-induced mitogenic response was inhibited to 65 and 15% of the control value by HAA at the concentrations of 10(-4) and 10(-3) M, respectively. HAA also inhibited phytohemagglutinin P and lipopolysaccharide-induced responses at the same concentrations. The pattern of inhibition of mitogen-induced responses by HAA at higher concentrations was found to be almost similar to that of dibutyryl cyclic AMP (DbcAMP). Both HAA and DbcAMP also inhibited the blastogenesis of spleen cells in one way mixed lymphocyte reaction.
    No preview · Article · Apr 1990 · Research communications in chemical pathology and pharmacology
  • Koichi Ueno · Anutosh Ranjan Saha · Haruo Kitagawa · Tetsuo Satoh
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    ABSTRACT: Heptaminol AMP amidate (HAA), a nucleotide derivative, was found to elevate the intracellular cyclic AMP (cAMP) level of cultured mice spleen cells in a time- and dose-dependent manner. Theophylline and imidazole, when added to the spleen cell culture simultaneously with HAA, respectively caused a further rise and a fall of the cAMP level increased by HAA alone. When comparatively higher doses of the T cell mitogen concanavalin A (Con A) were used in the culture, Con A-induced cell proliferation was mildly inhibited in the culture of spleen cells pooled from HAA administered mice in comparison to the culture of spleen cells pooled from saline treated mice. On the other hand, when another T cell mitogen phytohemagglutinin P (PHA) was used in different concentrations in the culture, there was a trend of enhanced cell proliferation in the culture of spleen cells pooled from HAA administered mice in comparison to the responses in the culture of spleen cells pooled from saline treated mice. The present results supported the previous findings that HAA-mediated immunopotentiation was closely related with a cAMP level elevating property of HAA, and the compound also enhanced the function of helper T cells.
    No preview · Article · Apr 1990 · The Japanese Journal of Pharmacology
  • M Kubota · K Ueno · M Yamano · H Kitagawa
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    ABSTRACT: It has been known that many antidepressant drugs which have serotonin (5-HT) antagonistic activities and 5-HT antagonists can induce the reduction of 5-HT2 receptor binding by their acute or successive administration. We investigated the effects of repeated treatment with 5-HT agonists on 5-HT2 receptors in rat cerebral cortex. We used citalopram as selective 5-HT uptake inhibitor, 5-hydroxytryptophan as 5-HT precursor, and 5-methoxy-N,N'-dimethyltryptamine as 5-HT2 agonist. The 5-HT2 receptor density was decreased by repeated treatment with these respective drugs. So it may be supposed that the reduction of 5-HT2 receptor binding is induced not only by 5-HT antagonists but also by 5-HT agonists.
    No preview · Article · Oct 1989 · Yakubutsu, seishin, kōdō = Japanese journal of psychopharmacology
  • H Kawamoto · K Ueno · C K Li · H Kitagawa · S Ohmori · T Igarashi
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    ABSTRACT: The effects of a minor tranquilizer, zopiclone, on endocrine system in male rats were assessed to clarify the mechanisms whereby large doses of zopiclone may induce testicular damage. 1) Zopiclone had no significant effect on plasma and tissue levels of hormones of the hypophyseo-gonadal or -thyroid system in rats given 10, 100 and 250 mg/kg/day orally for 28 days. 2) Rats given zopiclone in doses of 10 and 100 mg/kg/day orally for 14 days had lowered serum levels of PGE2 and PGF2 alpha but the testicular PGF2 alpha concentration remained unchanged. Therefore, oral administration of high doses of zopiclone to rats has no evident influence on endocrine system related to male reproduction. And these findings support our previous paper that repeated dose of zopiclone cause no significant change in plasma or epididymal TS levels, nor to any change in lipid peroxidation in testicular tissues.
    No preview · Article · Jun 1989 · Research communications in chemical pathology and pharmacology
  • H Kitagawa · F Takeda · H Kohei
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    ABSTRACT: The change in the endothelial function by the application of 0.6 N HCl and the effects of endothelium-derived relaxing factor (EDRF) inhibitors and nitrites on HCl-induced lesions were studied to clarify the effect of EDRF on gastric lesions in rats. The EDRF-induced increase in the gastric mucosal hemodynamics induced by vagal stimulation or intra-arterial administration of acetylcholine was inhibited by the EDRF inhibitors or removal of endothelial cells. Topical application of 0.6 N HCl on the exposed gastric mucosa abolished the response of the mucosal hemodynamics to acetylcholine or vagal stimulation. Gastric lesions induced by 0.45 N HCl were enhanced by EDRF inhibitors or removal of endothelial cells from gastric submucosal arterioles.
    No preview · Article · Feb 1989 · Scandinavian journal of gastroenterology. Supplement
  • H Nishiwaki · F Takeda · H Kitagawa · H Kohei
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    ABSTRACT: The roles of gastric acid and motility in gastric mucosal lesion formation induced by water-immersion stress were studied pharmacologically in rats. Gastric acid secretion and motility increased markedly during water-immersion, and mucosal lesions were formed. Cimetidine inhibited the increase in gastric acid secretion, but papaverine inhibited the increases in both acid secretion and motility. Both agents prevented the formation of mucosal lesions. In acid perfused rats, the increase in motility and lesion formation induced by water-immersion stress were prevented by papaverine, but not by cimetidine. These results suggest that the increases in both acid secretion and motility play important roles in the formation of mucosal lesions induced by water-immersion stress in rats.
    No preview · Article · Feb 1989 · Scandinavian journal of gastroenterology. Supplement
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    ABSTRACT: Heptaminol AMP amidate (HAA), a newly developed nucleotide derivative, was found to restore the immunosuppression in mice due to the induction of suppressor T (Ts) cells by concanavalin A (Con A) (50 micrograms/body). HAA also inhibited Con A-mediated in vitro induction of Ts cells. On the contrary, the administration of HAA in mice primed with keyhole lympet hemocyanin (KLH) (30 micrograms/body) caused an enhanced induction of antigen specific helper T (Th) cells. Effects of HAA on Ts and Th cells were found to be dependent on their level of induction. The administration of HAA also increased the spleen cell number and augmented the plaque forming cell response to some extent in cyclophosphamide treated mice. The present results suggested that HAA-mediated immunopotentiation was possible by a combined suppressive effect on Ts cells and enhancing effect on Th cells.
    No preview · Article · Jan 1989 · The Japanese Journal of Pharmacology
  • S Ohmori · T Misaizu · M Kitada · H Kitagawa · K Igarashi · S Hirose · Y Kanakubo
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    ABSTRACT: This is the first report for the hepatic lipid peroxide lowering effect of spermine in vivo. The influence of administration of polyamines on hepatic lipid peroxide level has been investigated by using normal or carbon tetrachloride (CCl4)-treated rats. Spermine was found to lower the hepatic lipid peroxide level most efficiently among polyamines used in CCl4-treated rats. In addition, the extent of liver enlargement caused by CCl4 treatment was reduced by spermine administration. Lipid peroxide lowering effect of spermine was also observed in normal rats. Hepatic spermine content was significantly increased in both normal and CCl4-treated rats after administration of spermine. Clear inverse relationship between the content of lipid peroxide and the concentration of spermine was observed. In reconstituted system containing NADPH-cytochrome P-450 reductase and extracted hepatic microsomal lipid, spermine inhibited the NADPH-dependent lipid peroxidation effectively at the concentration of 0.1 mM. From these results, we concluded that spermine exerted an inhibitory effect of lipid peroxidation in vivo as well as in vitro.
    No preview · Article · Dec 1988 · Research communications in chemical pathology and pharmacology
  • L H Wee · K Ueno · H Takeda · K Soma · H Kitagawa · T Satoh
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    ABSTRACT: The effects of eicosapentaenoic acid (EPA) on the humoral immune response in fat free diet-fed (FF) mice were studied. The lowered anti-SRBC PFC activity of ICR male FF mice was restored in a dose-dependent manner when EPA was administered orally at doses of 60-360 mg/kg/day for 20 days. In in vitro experiments, EPA similarly enhanced anti-SRBC PFC activity but did not affect the response against lipopolysaccharide. Furthermore, EPA did not cause any substantial effect on T suppressor cell activity induced by Concanavalin A in vitro. On the other hand, T helper cell activity induced by keyhole limpet hemocyanin was augmented. From these results, it is suggestive that EPA caused immunopotentiation to FF mice at least partially by an enhancement of T helper cell activities.
    No preview · Article · Nov 1988 · Research communications in chemical pathology and pharmacology
  • S Ohmori · M Kitada · A Hamada · T Igarashi · K Ueno · Y Kanakubo · H Kitagawa
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    ABSTRACT: NADPH-cytochrome P-450 reductase was purified to 30.8 units/mg from monkey liver microsomes. The purified reductase showed one major protein band (78,000) and two minor ones (58,000 and 20,000) on analysis by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Monkey, rat, and guinea pig reductases were not immunochemically identical to each other judged from Ouchterlony double diffusion analysis and immunotitration with regard to NADPH-cytochrome c reductase activity.
    No preview · Article · Sep 1988 · Biochemistry international
  • K Takanuki · T Igarashi · K Hata · H Hori · T Shibata · H Kitagawa · T Satoh · S Inayama
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    ABSTRACT: The effects of nitroimidazoles as radiosensitizers on intracellular glutathione (GSH) level were investigated in rat isolated hepatocytes. Dinitroimidazoles have lowered almost completely GSH level during the incubation for 30 min under oxic (95% O2+5% CO2) condition, while mononitroimidazoles had scarcely affected. In the case of hypoxic (95% N2+5% CO2) condition, however, 2-nitroimidazoles, not 4-nitroimidazoles, as well as 2,4- and 4,5-dinitroimidazoles have caused the significant depletion of GSH. This suggests that nitro group in the 2-position of imidazoles may be responsible for the GSH depletion under hypoxia. Especially, 2-nitroimidazole-1-acetohydroxamic acid (KIH-801) was found to be the most potent GSH depletor only under hypoxic, not oxic conditions, and might be useful for the new hypoxic cell radiosensitizer instead of misonidazole.
    No preview · Article · Aug 1988 · Biochemistry international
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    ABSTRACT: Heptaminol AMP amidate (HAA), a newly developed derivative of 5'-AMP, was found to potentiate the in vitro primary humoral immune response against T cell-dependent antigen, sheep red blood cells, when HAA was present in the early phase of spleen cell culture. Such a potentiating effect was not found against T cell-independent antigens such as lipopolysaccharide (LPS), trinitrophenylated (TNP)-LPS and TNP-Ficoll. The pattern of HAA-mediated immunopotentiation was similar to that of dibutyryl cyclic AMP. When HAA was added to the culture simultaneously with theophylline and imidazole, the immunopotentiating effect of HAA was further augmented and suppressed, respectively. The present results suggested that HAA-mediated immunopotentiation might be in some way related to the intracellular level of cyclic nucleotides in the early phase of culture.
    No preview · Article · Jun 1988 · The Japanese Journal of Pharmacology
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    ABSTRACT: The effect of carbon tetrachloride (CCl4) treatment on plasma and liver cytosolic glutathione S-transferase (GST) activities was investigated in rats. CCl4 was intraperitoneally administered at a dose of 0.5 ml/kg. The elevation of plasma GST activity paralleled the increase of plasma glutamate pyruvate transaminase activity after the administration of CCl4. Liver cytosolic GST activities were significantly decreased by CCl4 treatment. To establish the relationship of plasma GST with liver cytosolic isozymes, Western blot analysis using antibodies against cytosolic GST 1-2 and 3-4 was performed. The Western blots showed the existence of GST 1-2 and 3-4 in plasma at 24 hr after CCl4 treatment. The data thus strongly suggest that cytosolic GSTs are lost from the liver to plasma as a consequence of liver damage. The Western blot analysis of plasma GST may be useful for monitoring liver damage.
    No preview · Article · Apr 1988 · The Japanese Journal of Pharmacology
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    ABSTRACT: The in vitro effect of trichosanic acid (TCA; C18:3, omega-5), a major component of Trichosanthes japonica, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. TCA dose-dependently suppressed platelet aggregation of platelet rich plasma and washed platelets. TCA decreased collagen (50 micrograms/ml)-stimulated production of thromboxane B2 (TXB2) and 12-hydroxyhepta-decatrienoic acid (HHT) in a dose-dependent manner, while that of 12-hydroxyeicosatetraenoic acid (12-HETE) was rather enhanced. The conversion of exogenously added [14C]AA to [14C]TXB2 and [14C]HHT in washed platelets was dose-dependently reduced by the addition of TCA, while that to [14C]12-HETE was increased. Similar observations were obtained when linolenic acid (LNA; C18:3, omega-3) was used. These results suggest that TCA may decrease TXA2 formation in platelets, probably due to the inhibition of cyclooxygenase pathway, and thereby reduce platelet aggregation.
    No preview · Article · Mar 1988 · Prostaglandins Leukotrienes and Essential Fatty Acids
  • K Ueno · H Masumura · H Kawamoto · H Kitagawa
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    ABSTRACT: The effects of oral administration of ketoprofen, naproxen, flurbiprofen (1.0 mg/kg), indomethacin (1.0 and 3.0 mg/kg), and acetylsalicylic acid (100 mg/kg) on release of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) from isolated pregnant rabbit uterus were studied comparatively. Ketoprofen, indomethacin, flurbiprofen, naproxen and acetylsalicylic acid reduced the release of PGF2 alpha and PGE from the isolated rabbit uterus. The inhibitory effect was most profound with flurbiprofen, followed, in order, by naproxen, ketoprofen, indomethacin and acetylsalicylic acid. A comparative study with intramuscular ketoprofen (0.1, 1.0 and 3.0 mg/kg) was also carried out. The inhibitory effect of ketoprofen on uterine PGF2 alpha and PGE release with intramuscular route was about 10 times more profound than that with oral route.
    No preview · Article · Feb 1988 · Research communications in chemical pathology and pharmacology

Publication Stats

1k Citations
209.99 Total Impact Points

Institutions

  • 1974-1993
    • Chiba University
      • Faculty of Pharmaceutical Sciences
      Tiba, Chiba, Japan
  • 1987
    • Chiba University Hospital
      Tiba, Chiba, Japan
  • 1982-1983
    • Hokuriku University
      Kanazawa, Ishikawa, Japan