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H Fujimura

Publications and source records attributed to H Fujimura.

At least 235 records · Page 13Linked to original sources
PubMed1982

Elimination of GTP biphasic regulation of synaptosomal adenylate cyclase by manganese and solubilization.

Effects of divalent cations and solubilization with Lubrol-PX were studied on guanine nucleotide regulation of synaptosomal adenylate cyclase activity of the rat caudate nucleus. In the presence of Mg2+, both GTP and Gpp(NH)p exerted biphasic actions on the membrane-bound adenylate cyclase activity. The K0.5 value for the GTP stimulation of the cyclase was 47 nM, and the value for the GTP inhibition was 4.5 microM. One hundred microM dopamine selectively enhanced the stimulatory phase of the GTP action, whereas 10 microM morphine selectively enhanced the inhibitory phase of the GTP action. When Mg2+ was replaced by Mn2+, the inhibition of the membrane-bound adenylate cyclase by these nucleotides and morphine was completely abolished; but the catalytic activity of adenylate cyclase was not impaired. These results suggest that the inhibitory action of GTP is responsible for the morphine inhibition of synaptosomal adenylate cyclase. Lubrol-solubilized adenylate cyclase prefered Mn2+ to Mg2+ for its activity. The stimulation of adenylate cyclase by either GTP or Gpp (NH)p was eliminated in the Sepharose 6B-fractionated solubilized preparation in the presence of either Mg2+ or Mn2+. Ten mM NaF also failed to activate the fractionated adenylate cyclase. In the fractionated solubilized preparation, GTP and Gpp(NH)p failed to inhibit adenylate cyclase. These results indicate that GTP and Gpp(NH)p are unable to inhibit the resolved catalytic unit of the synaptosomal adenylate cyclase.

Adenylyl Cyclases↗
PubMed1982

[Cephem antibiotics and alcohol metabolism: (1) Disulfiram-like reaction resulting from intravenous administration of cephem antibiotics].

Fifty to 500 mg/kg doses of the cephem antibiotics were intravenously injected to male rats twice a day for 3 days. After the last injection, the rats were fasted for 17 hours and then orally administered 2 g/kg or 20% ethanol. The blood levels of ethanol and acetaldehyde (AcH) were determined by gas chromatography. Cefotiam, cefsulodin, and cefazolin did not affect the blood levels of ethanol and AcH as compared with those of the control. Cefmetazole, cefamandole, and cefoperazone did not change the blood ethanol level, but these antibiotics increased the blood AcH level dose-dependently. Cefamandole was especially able to sustain a high blood AcH level for over 8 hours. All of the antibodies which increased blood AcH levels contain the 1-methyl-1H tetrazole-5-thiol (TZ) group in their chemical structure. Intravenous injection of TZ caused a significant increase of the blood AcH level without influence on the blood ethanol level. 1-(2-Dimethyl-aminoethyl 1H-tetrazole-5-thiol (MTZ), the functional group which is contained in cefotiam, did not affect the blood levels of ethanol and AcH. These results suggested that the disulfiram-like reaction of cefmetazole, cefamandole, and cefoperazone results from an increase of the blood AcH level, and the 3-substituent group in in aminocephalosporanic acid, i.e., TZ, is an important factor for the reaction.

Acetaldehyde↗
PubMed1982

[Inhibitory effect of TN-762 (suprofen) on platelet aggregation].

Inhibitory effects of TN-762 (suprofen), ketoprofen, and indomethacin on rat or rabbit platelet aggregation were examined. Of these compounds tested, Suprofen showed the most potent effect on platelet aggregation in vitro, especially in AA-induced rabbit platelet aggregation (IC50 = 0.01 microM). Suprofen showed an inhibitory effect similar to that of ketoprofen and indomethacin on rat platelet aggregation ex vivo. The lethal effect of AA in the rabbits was protected by suprofen (0.05 mg/kg p.o.) at concentrations lower than the other compounds. Similar to the compounds, suprofen had little effect on the PG I2 synthesis in the rat aorta. In order to test the direct effects of these compounds on the platelet avoiding the effects of other plasma components, gel-filtrated rat platelets were used. All tested compounds showed similar inhibitory effect. To investigating the interaction of these compounds with the lipid bilayers, we used the liposome as a model membrane. The tested compounds inhibited liposome aggregation induced by 4 mM Ca2+. In this experiment, the interaction of suprofen with the lipid bilayers was shown.

Adenosine Diphosphate↗
PubMed1982

[Effect of tiemonium iodide on colonic motility in dogs].

Effects of tiemonium iodide (tiemonium, 20 micrograms/kg), mepenzolate bromide (mepenzolate, 20 micrograms/kg), butylscopolamine bromide (butylscopolamine, 50 micrograms/kg) and atropine sulfate (atropine, 10 micrograms/kg) on the colonic motility in dogs were evaluated using a balloon method. The frequency of the wave motion was analyzed by fast Fourier transform, and the power spectra were obtained. The value of the first term of the power spectrum is regarded as an indication of the colonic tonus. Inhibitory effects of tiemonium on both the normal proximal colonic motility and the accelerating motility induced by neostigmine metylsulfate (neostigmine, 50 micrograms/kg) were equal to those of butylscopolamine. In the case of distal colonic motility, tiemonium showed potent mepenzolate-like inhibition. When the drugs were injected into the veins after administration of PGF2 alpha (10 micrograms/kg), all of the drugs depressed the colonic constriction induced by PGF2 alpha. The colonic motility was not restored by the administration of tiemonium or mepenzolate before the injection of PGF2 alpha, but such an effect was not observed in the case of butylscopolamine and atropine. It is suggested that tiemonium shows an extensive inhibition on the colonic motility in the mode of mepenzolate-like action and by some additional mechanism.

Animals↗
PubMed1982

[Anti-inflammatory, analgesic and antipyretic activities of alpha-(p-thenoylphenyl)-propionic acid (TN-762) (author's transl)].

We reported in our previous paper that TN-762, a potent inhibitor of prostaglandin biosynthesis, has marked inhibitory activity on acute experimental inflammation. In this paper, the anti-inflammatory, analgesic, and antipyretic activities of TN-762 were assessed in animal models, and compared with those of indomethacin, ketoprofen and ibuprofen. TN-762 inhibited the sustained paw edema induced by mustard in rats during administration for 3 days, but after final administration, the inhibitory activity was decreased rapidly and was less then that of ketoprofen and indomethacin. TN-762 also inhibited the proliferation of granuloma induced by means of cotton pellet and granuloma pouch methods, and the adjuvant arthritis in rats. The inhibitory activity of the compound on inflammatory proliferation was more potent than that of ibuprofen, but slightly less than that of ketoprofen and less than about 1/10 times that of indomethacin. Indomethacin markedly inhibited the body weight gain at a high dose, while TN-762 did not affect it. Therefore, TN-762 was proven to have an inhibitory effect on subacute and chronic inflammation at low doses without toxic effects, but the compound appeared to have a less of an inhibitory effect on secondary or late stages of inflammation than on primary stage inflammation. TN-762 inhibited the acute paw edema induced by nystatin, and the inhibitory activity was the same as that of ketoprofen and indomethacin. The pathogenesis of nystatin edema has been considered to be due to lysosomal labilization. This result suggests that TN-762 has a potent membrane stabilizing action which is considered to be one of the necessary mechanisms in anti-inflammatory action. On the other hand, TN-762 showed the same potent analgesic effect as ketoprofen and indomethacin as observed by the acetic acid writhing and modified Haffner's methods in mice and by the Randall-Selitto's method in rats. However the antipyretic effect of TN-762 was significantly less than that of ketoprofen and indomethacin.

Analgesics↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (II). Anti-allergic action (author's transl)].

The anti-allergic effect of Mequitazine (LM-209) which was found to have an anti-histaminic activity was investigated in guinea-pigs. The inhibitory activities of LM-209 on the Schultz-Dale reaction and ileum contraction by some mediators released from the sensitized guinea-pig lung were the same as those of clemastine fumarate (CL) but with 5 times the potency. LM-209 and CL, but these activities were less potent than in the case of disodium cromoglycate. The various anaphylactic reactions mediated by IgG in guinea-pigs were inhibited by LM-209, CL and chlorpheniramine maleate (CPM). The homologous PCA mediated IgE in rats was also inhibited by LM-209, CL and CPM, but the duration of the action with LM-209 was markedly longer. In experimentally-induced asthma, the decrease of respiratory rate and volume was significantly inhibited by LM-209, but was not affected by CL. Thus, LM-209 seems to inhibit the allergic reaction mainly by an antagonistic action on allergic mediators.

Anaphylaxis↗
PubMed1981

Inhibition of adenylate cyclase by GTP and its modulation by opiate receptor in rat caudate nucleus.

Morphine inhibited the adenylate cyclase activity of the crude synaptosomal fraction of the rat caudate nucleus in the presence of BTP, GDP, Gpp(NH)p or ITP. The purine nucleotides themselves had an inhibitory action on the enzyme. Beta-endorphin and Met-enkephalin also inhibited the enzyme in the presence of GTP. The GTP-dependent in inhibitory action of morphine was blocked by naloxone. Various opiates and opioid peptides inhibited the enzyme by up to approximately 20 per cent in the presence of GTP. The relative potency was in higher order of levorphanol greater than beta-endorphin greater than Met-enkephalin greater than morphine greater than pentazocine. Levorphanol was about 50,000 times as potent as its biologically inactive enantiomer, dextrorphan. Morphine enhanced the inhibitory actions of GTP and GTPase-resistant Gpp(NH)p on the adenylate cyclase activity. These results suggest that GTP plays an important role in the regulation of adenylate cyclase activity in the rat caudate nucleus and that the occupation of opiate receptor by agonists inhibits the enzyme through an actual increase in the inhibitory action of GTP, rather than a suppression of the enzymatic degradation of GTP.

Adenylyl Cyclase Inhibitors↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application.

Analgesics↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (I). Antagonistic actions of chemical mediators (author's transl)].

Antagonistic activities of Mequitazine (LM-209) on chemical mediators and in particular histamine were investigated in guinea-pigs, mice and rats. The antagonistic activity of LM-209 for histamine in the isolated ileum and trachea of guinea-pigs was less potent than that for clemastine fumarate (CL) and chlorpheniramine maleate (CPM) while that for acetylcholine was more potent than CL and CPM. Moreover, the antagonistic activities of these three compounds on serotonin and bradykinin were almost equipotent in the excised ileum. Using a modified Konzett-Rössler method, the bronchodilating effect of LM-209 (p.o.) for histamine was same as CL, but that for acetylcholine was more potent than CL and CPM. The protective activity of LM-209 (p.o.) on acute death induced by histamine and metacholine in mice was the same as CL, but the duration of the anti-histaminic action was markedly longer than CL. LM-209 given orally inhibited markedly the increased vascular permeability by histamine in rats and the diarrhea by 5-HTP in mice, but did not affect on the histamine-induced ulcer in guinea-pigs. From these results, LM-209 appears to have potent and long acting antagonistic activity on various chemical mediators.

Acetylcholine↗
PubMed1981

[Effect of alpha-(p-thenoylphenyl)-propionic acid (TN-762) on acute inflammatory reactions and prostaglandin biosynthesis].

A series of compounds with the general structure of phenylpropionic acid was originally synthesized for anti-inflammatory screening. The title compound, TN-762, showed marked anti-inflammatory and analgesic activities and was less toxic. This compound was the same as suprofen which was reported by Janssen to have potent anti-inflammatory and anti-writhing activities. Effects of TN-762 on acute inflammatory reactions and prostaglandin biosynthesis were investigated in animal models and findings compared to those of ketoprofen and indomethacin. TN-762 showed a dose-dependent inhibition at low doses of 5-20 mg/kg, p.o. on an increased vascular permeability induced by histamine in rats and by acetic acid in mice and carrageenin-induced paw edema in rats. The anti-inflammatory activity of TN-762 was much the same as that of ketoprofen and indomethacin. The inhibitory effect of TN-762 on carrageenin-induced paw edema was not affected by successive administration for 14 days and/or by adrenalectomy. The compound was more active than the two reference compounds in inhibiting ultraviolet erythema in guinea pigs. TN-762 inhibited markedly the arachidonic acid potentiation of carrageenin-induced edema in rat paw, the sudden death following intraveneous administration of arachidonic acid to rabbits and the diarrhea produced by endotoxin in mice, all considered to be induced by biosynthetic prostaglandins. The activities of TN-762 were the same or were more potent than those of ketoprofen and indomethacin. On the contrary, the ulcerogenic activity of TN-762 on the gastrointestinal tract in rats was significantly less than that of ketoprofen and indomethacin. From the above results, TN-762 proved to be a potent inhibitor of acutely-induced inflammation and of prostaglandin biosynthesis, however, the ulcerogenic effects were comparatively diminished.

Animals↗