The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 33 , Issue 4
Showing 1-27 articles out of 27 articles from the selected issue
  • Yasumitsu YAMANAKA, Toshinori YAMAMOTO, Toru EGASHIRA
    1983 Volume 33 Issue 4 Pages 717-723
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of cephem antibiotics, which have a tetrazolethiol side chain, on rat liver mitochondrial aldehyde dehydrogenases (ALDH) were investigated in vitro and in vivo. The antibiotics tested were cefmetazole (CMZ), cefamandole (CMD), cefotiam (CTM), cefoperazone (CPZ) and latamoxef (LMOX). The antibiotics inhibited low-Km ALDH activity by 17-30% at 5 mM in vitro. The degrees of inhibition were in the order: CMZ=CTM=CMD>LMOX>CPZ. Disulfiram inhibited the enzyme activity by 50% at approx. 40, μM. The antibiotics (except CTM) at a dose of 1, 000 mg/kg i.v. inhibited the low-Km ALDH activity by 36-52% of the control 24 hr after pretreatment, but did not alter the high-Km ALDH activity. The degrees of inhibition were in the order: LMOX=CMD>CPZ>CMZ. Disulfiram at a dose of 300 mg/kg p.o. markedly inhibited the low-Km ALDH activity, but did not alter the high-Km ALDH activity. The blood acetaldehyde levels during ethanol metabolism were elevated 1.3-2.6 times in rats treated with the cephem antibiotics (except CTM) for 24 hr at a dose of 1, 000 mg/kg i.v. The degrees of elevation at 1 hr after ethanol injection were in the order: LMOX>CMD>CPZ>CMZ. The present experiments demonstrated that the rise in blood acetaldehyde levels coincided with the inhibition rates of the low-Km ALDH activity by the cephem antibiotics.
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  • Manabu NEGISHI, Atsushi ICHIKAWA, Kenkichi TOMITA
    1983 Volume 33 Issue 4 Pages 725-734
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Kinetic analysis of Ca2+ metabolism in mastocytoma P-815 cells showed that at non-cytotoxic and growth-inhibitory concentrations (<10μg/ml), the calcium ionophore A23187 did not affect the rate constant (36.2 min-1) or the compartment size (8.32 nmol/106 cells) of the fast phase of calcium exchange at the cell surface. In contrast, A23187 (1 to 10μg/ml) dose-dependently increased the compartment size of slow phase I of the intracellular calcium uptake from 0.54 to 2.39 nmol/106 cells without affecting the rate constant (2.38 min-1). In addition, A23187 (5 to 10, μg/ml) produced an additional compartment [slow phase II] with a rate constant of 0.25 min-1 and increased its compartment size from 0.42 to 1.26 nmol/106 cells. A23187 (10μg/ml) in the presence of Ca2+ (0.9 mM) non-competitively inhibited the membrane transport of amino acids, glucose and nucleosides; and it also reduced the cellular ATP level and the membrane fluidity. Apparently, A23187 inhibits the growth of mastocytoma cells by elevating the intracellular concentration of Ca2+, which in turn reduces the membrane fluidity and the carrier-dependent as well as the active membrane transport of various nutrients required for cellular growth.
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  • Nobuo KAWABATA, Seiyu SUGIYAMA, Tsukasa KUWAMURA, Tetsuo SATOH, Haruo ...
    1983 Volume 33 Issue 4 Pages 735-747
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The plasma and liver concentrations of both 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and 5-fluorouracil (5-FU), an active metabolite of FT, increased very markedly after administration of FT (500 mg/kg, p.o.) combined with L-cysteine (L-CYS, 500 mg/kg, i.p. or p.o.) when compared to FT alone in rats. On the other hand, the oral acute toxicity of FT was also enhanced with the combined administration of FT and L-CYS. There was no difference in the in situ absorption rate of FT from the small intestine between rats treated with L-CYS (500 mg/kg, i.v.) and vehicle-treated controls. The inhibition of the disappearance of FT and the increase of the formation of 5-FU was observed in vitro after incubation of FT with liver microsomes from rats treated with L-CYS (500 mg/kg, p.o.) when compared to vehicle-treated controls. The presence of L-CYS significantly inhibited the in vitro degradation of 5-FU by non-treated rat liver homogenate. In the drug metabolizing enzyme activity of rat liver microsomes, aniline p-hydroxylase activity was inhibited, but aminopyrine N-demethylase activity was conversely activated by the combined administration of FT and L-CYS, but not by FT alone; furthermore, no change of cytochrome P-450 content was observed. In sarcoma 180 bearing mice, the oral antitumor activity of FT in combination with L-CYS (500 mg/ kg, i.p. or p.o.) was about 1.1-2.0 times higher than that of FT alone. It was concluded from these findings that the drug metabolizing enzymes in liver involved in the conversion of FT into an active metabolite, 5-FU, are influenced by the combined administration of FT and L-CYS to give an increased organ level of 5-FU; and this resulted in the enhancement of the antitumor activity of FT.
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  • Michio TERAI, Shinji USUDA, Izumi KUROIWA, Osamu NOSHIRO, Hiroo MAENO
    1983 Volume 33 Issue 4 Pages 749-755
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Effects of YM-09151-2 and five other neuroleptics (haloperidol, spiperone, chlorpromazine, sulpiride and clozapine) on the binding of [3H]-ligands to nine different receptors (α1-adrenergic, α2-adrenergic, β-adrenergic, muscarinic, D2-dopaminergic, H1-histaminergic, 5HT1-serotonergic, 5HT2-serotonergic and opiate receptors) and on dopamine-sensitive adenylate cyclase were determined using brain membranes in the rat, guinea-pig and dog. The affinity of YM-09151-2 for D2-receptors with a Ki value of 0.1 nM was more than 1000-times higher than that for the other receptors and dopamine-sensitive adenylate cyclase, and it was the greatest among the nueroleptics tested.
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  • Ryuji TAKEDA, Yasunori MOMOSE
    1983 Volume 33 Issue 4 Pages 757-764
    Published: 1983
    Released: November 07, 2006
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    Effects of ethanol on adrenergic neuromuscular transmission were investigated in the isolated vas deferens of the guinea-pig. The contractile responses to adrenergic nerve stimulation were depressed by ethanol in a concentration-dependent, reversible manner at a concentration range between 25 and 500 mM. Ethanol also depressed the contractions induced by exogenous noradrenaline. The resting membrane potentials recorded intracellularly from the smooth muscle cells were not affected by the alcohol. The excitatory junction potentials (EJPs) evoked by nerve stimulation decreased in amplitude, but the facilitation phenomena observed with repetitive stimulation remained unaltered. Ethanol slightly increased the frequency of the spontaneous EJPs, but decreased their amplitude. The extracellularly recorded action potentials from the small sympathetic nerve bundles innervating the vas deferens were suppressed by high concentrations of ethanol (more than 200 mM). These results indicate that ethanol inhibits adrenergic neuromuscular transmission in the vas deferens probably through depressing the sensitivity of the postsynaptic membrane to the transmitter and a block of axonal conduction in the presynaptic nerve terminals.
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  • Sumiko FUJINO, Hideki TSUKADA
    1983 Volume 33 Issue 4 Pages 765-773
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    To clarify the cause of hypersensitivity to digitoxin, an experiment was carried out with cats. The most potent hypersensitivity to digitoxin has been observed 48 hr after the injection of a loading dose. However, 1 hr after this injection, the cats failed to show the hypersensitivity. One, 24 and 48 hr after the injection of 3H-digitoxin, the contents of digitoxin and its metabolites in subcellular fractions of hearts were measured. Digitoxin contents in microsomal fractions 48 hr after the injection only slightly decreased, while those in mitochondrial and nuclear fractions markedly decreased as compared with the check at 1 hr. An increase of sodium ions and a decrease of potassium ions in the hearts were seen 48 hr after the injection. These facts may be related to the cause of hypersensitivity.
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  • Akihiro TOBE, Mitsuo EGAWA, Rie NAGAI
    1983 Volume 33 Issue 4 Pages 775-784
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    To predict the possible activity on memory disorders, the effect of MCI-2016 was compared with those of physostigmine, choline chloride, methamphetamine, apomorphine, imipramine and calcium hopantenate by applying scopolamine-induced deficit of spontaneous alternation behavior (scopolamine-SA) as a proposed animal model for senile dementia. MCI-2016 was shown to improve the scopolamine-SA at doses of 25 to 100 mg/kg p.o. without producing any remarkable behavioral abnormalities. As for the effect of reference drugs, two types of cholinomimetic drugs (physostigmine and choline chloride) and methamphetamine were shown to be active. In the cases of physostigmine and methamphetamine, however, behavioral abnormalities were observed at those dose levels effective on scopolamine-SA. MIC-2016 potentiated the effect of physostigmine on scopolamine SA at non active doses of 10 to 20 mg/kg p.o. In comparison with the deleterious effect of scopolamine on spontaneous alternation (SA) behavior itself, none of the test drugs except for imipramine were shown to disrupt the SA. Considering the disruptive or improving actions of various agents on SA or scopolamine-SA, it may be suggested that the present model is relatively sensitive to those drugs which affect the cholinergic mechanism either directly or indirectly. Mechanisms of the actions of MCI-2016 and methamphetamine were also discussed with reference to possible involvement of cholinergic mechanisms.
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  • Naohisa ISHIKAWA, Kazumi TAKI, Yasuo HOJO, Yasumichi HAGINO, Tatsuro S ...
    1983 Volume 33 Issue 4 Pages 785-794
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Our new method for the graphical analysis of drug effects in the dog heartlung preparation was extended to pulmonary circulation. The equilibrium points, at which the cardiac output (CO) curve and venous return (VR) curve cross each other in the right atrial pressure (RAP)-CO and left atrial pressure (LAP)-CO relations, were directly recorded on two X-Y recorders. The VR curves were obtained by inducing cardiac fibrillation and simultaneously occluding the pulmonary arterial trunk. The competence test, which was utilized previously for recording the CO curve in the RAP-CO relation (Ishikawa et al., 1978), was confirmed to be a good procedure for the CO curve in the LAP-CO relation. During the competence test, the mean pulmonary pressure (Pmp) which is the intercept of the pulmonary VR curve on the LAP axis in the LAP-CO relation was changed as much as the change in the systemic reservoir blood level, with little change in the slope of the pulmonary VR curve. When the reservoir blood level was 100 mm above the superior vena cava and the aortic pressure was 70 mmHg (control), the Pmp value was 136±7 mmH2O (n=24). The slope of the pulmonary VR curve was not so different from that of the systemic VR curve in RAP-CO relation. Raising aortic pressure to 100 mmHg caused a shift of the equilibrium point to the right and slightly downwards, increased the Pmp value by 42.9±9.9 mmH2O (ΔPmp) and decreased the reservoir blood volume by 26.2±6.4 ml (ΔV). The ratio ΔV/ΔPmp was 0.66±0.11 ml/mmH2O. The continuous infusion of norepinephrine 4 μg/min caused a shift of the equilibrium point to the left and upwards, decreased the Pmp value by 67.1±19.1 mmH2O and increased the reservoir blood volume by 35.3±7.2 ml. The ratio ΔV/ΔPmp was 0.56±0.16 ml/ mmH2O. The continuous infusion of 5-hydroxytryptamine at the rate of 60 μg/min caused a shift of the equilibrium point almost vertically and downwards, increased Pmp value by 34.8±3.2 mmH2O and decreased the reservoir blood volume by 45.8±10.1 ml. The ratio ΔV/ΔPmp was 0.88±0.10 ml/mmH2O
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  • Yoko ANIYA, Kichihiko MATSUSAKI
    1983 Volume 33 Issue 4 Pages 795-801
    Published: 1983
    Released: November 07, 2006
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    Enhancement of aniline hydroxylation by Habu snake venom was studied in vitro. The fraction which was isolated from Habu venom through column chromatography caused the enhancement of aniline hydroxylation of hepatic microsomes obtained from untreated rats. This fraction was heat stable and free from phospholipase activity. Enhancement of aniline hydroxylation was not clear in crude Habu venom or the unheated fraction, but appeared after heating of the fraction. This fraction enhanced aniline hydroxylation at low concentrations, followed by inhibition at high concentrations, but inhibited aminopyrine N-demethylation dose-dependently. Aniline hydroxylation was enhanced by the heated fraction at more than 1 mM aniline, and the enhancement was rather decreased at more than 10 mM aniline. The degree of the enhancement by the heated fraction increased with increasing pH.
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  • Yasuo MATSUMURA, Toshikatsu SHIMIZU, Yukihiro OHNO, Nobuaki MIYAWAKI, ...
    1983 Volume 33 Issue 4 Pages 803-810
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    This study was carried out to investigate the effect of lipid peroxidation in the renin granule fraction on renin release from the granules. Ascorbic acid was used to cause lipid peroxidation in the renin granule fraction prepared from rat kidney cortex homogenate. Renin activity was measured by radioimmunoassay and lipid peroxidation was estimated by means of the thiobarbituric acid test. Ascorbic acid, at the concentrations from 5 to 100 μM, produced a dose-dependent increase in lipid peroxidation during incubation of the renin granule fraction at 37°C for 30 min, accompanied by increased release of renin from the granules. On the other hand, dehydroascorbic acid showed no effects on lipid peroxidation and renin release. The simultaneous increases in lipid peroxidation and renin release induced by ascorbic acid in the renin granule fraction were markedly suppressed by the addition of disodium ethylenediaminetetra-acetic acid and antioxidants such as N, N'-diphenyl-p-phenylenediamine and hydroquinone. These findings indicate that lipid peroxidation in the renin granule fraction results in the stimulation of renin release from the granules.
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  • Hideyo OHSHIKA, Atsushi MIYAMOTO, Haruo TAKEMURA, Shinichi HATTA, Mamo ...
    1983 Volume 33 Issue 4 Pages 811-817
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The effect of repeated exposure to isoproterenol (ISO) in parotid tissue was investigated with regards to potassium release in response to a successive challenge of α- and β-adrenergic agonists. An increase in potassium release by epinephrine was potentiated in the parotid tissue from rats repeatedly administered ISO (3 mg/kg, three times daily for 3 days). On the other hand, a decrease in the release by ISO disappeared in ISO-pretreated glands. Cycloheximide and actinomycin D, administered with ISO, completely blocked the ISO-induced development of the enhanced response to epinephrine, but not that of the reduced response to ISO. After in vitro pretreatment with ISO, the potassium release induced by a successive dose of ISO was higher than the basal release of the electrolyte. The same treatment showed a tendency to increase the response to norepinephrine. The increased release induced by a challenge dose of ISO disappeared in the tissue from cycloheximide-treated rats. The ISO-induced increase of potassium release which was caused by ISO-pretreatment in vitro was inhibited by prazosin, but not by yohimbin and propranolol. These results suggest the possibility that the α-adrenergic response in parotid tissue might be potentiated by exposure to ISO.
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  • Hiroichi NAGAI, Takeshi NISHIYORI, Michio DAIKOKU, Akihide KODA
    1983 Volume 33 Issue 4 Pages 819-828
    Published: 1983
    Released: November 07, 2006
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    Effect of sodium copper chlorophyllin (SCC) on experimental allergic reaction was investigated. IgE antibody mediated reactions, homologous passive cutaneous anaphylaxis (PCA) in rats and the release of anaphylactic mediators (histamine and/or slow reacting substance of anaphylaxis (SRS-A)) from sensitized guinea pig lung tissues or rat peritoneal mast cells classified as a Type I reaction were clearly inhibited by SCC at a similar potency as N-(3', 4'-dimethoxy cinnamoyl) anthranilic acid (N-5'). The increase of vascular permeability in rat skin caused by autacoids or enzymes that participate in the Type I reaction was also inhibited by SCC. Type II or III, complement dependent, reactions including reversed cutaneous anaphylaxis (RCA) in rats and Forssman cutaneous vasculitis (FCV) in guinea pigs were inhibited by SCC. Prednisolone inhibited RCA in rats, but did not inhibit FCV in guinea pigs. Two experimental types of glomerulonephritis, nephrotoxic serum (NTS) nephritis in rats and immune complex nephritis in (NZW×NZB) F1 mice, in which Type II and III reactions might participate in the onset and the development of the disease, were slightly inhibited by SCC in terms of the biochemical changes of blood and urine parameters and histopathological scores. A moderate remission of the onset and development of these two experimental types of nephritis was recognized by the administration of prednisolone. Delayed hypersensitivity reaction as a Type IV reaction caused by sheep red blood cells (SRBC) in sensitized mouse footpad was not affected by SCC. Prednisolone clearly inhibited the SRBC induced footpad reaction in mice. IgM antibody production in mice and IgE antibody production in rats were not influenced by daily injection of SCC.
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  • Mineo KUNIHARA, Miyuki KANBAYASHI, Takao OHSHIMA
    1983 Volume 33 Issue 4 Pages 829-835
    Published: 1983
    Released: November 07, 2006
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    The present study was undertaken to examine how morphine changes food and water intake in non-fasted or fasted rats with different administration times. Morphine (1, 3 and 10 mg/kg) was intraperitoneally administered at 10:45 (light period) or 18:45 (dark period). Morphine increased food and water intake in non-fasted rats 2 hr after the administration during the light period, whereas the total daily intakes were decreased. In contrast, morphine decreased food and water intake in non-fasted rats during the dark period and in fasted rats during both the light and dark period. These results suggest that morphine disorders the baseline levels of feeding and water drinking of naive rats.
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  • Tetsuhiro KUBOTA, Arao UJIIE, Jun NAITO, Masayuki NAKAZAWA, Akihide KO ...
    1983 Volume 33 Issue 4 Pages 837-843
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    To investigate the mechanisms for the inhibition of IgE-mediated histamine release from rat peritoneal exudate cells (PEC) by N-5', we studied the relation between the inhibitory effect of N-5' on histamine release and the intracellular levels of adenine nucleotides such as ATP and cAMP. Evident histamine release was induced by the addition of specific antigen to rat PEC sensitized with IgE antiserum in vitro, and the release showed a maximum 30 sec after the antigen challenge. In the same time course as the histamine release, the intracellular levels of ATP and cAMP decreased. N-5' significantly inhibited the histamine release and a decrease in ATP level as a result of the antigen-antibody reaction. A decrease in cAMP level showed a tendency to be sup pressed by N-5'. Antigen-induced 14CO2 production for 6-14C-glucose in the sensitized PEC was 3 times that seen in the case without antigen. N-5' dramatically suppressed the accerelation in the production of 14CO2. Differing from the action of papaverine, the inhibitory effect of N-5' on the IgE-mediated histamine release from rat PEC was identical both in the presence or in the absence of glucose. N-5' scarcely affected the ATP level in the non-sensitized PEC in the glucose-free medium. On the other hand, N-5' inhibited the activity of Na+, K+-ATPase, one of the ATP-consuming enzymes, in a dose dependent fashion. From these results, it is presumed that the suppression of ATP utilization through the inhibition of Na+, K+-ATPase activity is involved in the inhibition of histamine release by N-5'. The relation between the inhibitory effect of N-5' on histamine release and both nucleotides was also discussed.
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  • Kosho AKUTAGAWA, Minoru MAKINO, Kenji ISHII
    1983 Volume 33 Issue 4 Pages 845-850
    Published: 1983
    Released: November 07, 2006
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    Effects of flurazepam, a benzodiazepine derivative, on Ca2+-Induced cardiostimulant contractile activity in normal Tyrode's solution and Ca2+-mediated contraction in K+-rich (19-22 mM) Tyrode's solution were investigated in electrically driven left atrial preparations isolated from guinea-pigs. In normal Tyrode's solution, flurazepam (1×10-6, 1×10-5 and 1×10-4 M) noncompetitively shifted the dose-response curves for CaCI2 downwards. In K+ (19 mM)-rich Tyrode's solution, flurazepam (3×10-5 M) decreased contractile amplitude time-dependently; and after addition of CaCl2 (final: 8 mM), contractile amplitude was increased time-dependently. In K++ (19 mM)-depolarized preparations, flurazepam (3×10-5 M) competitively shifted the dose-response curve for CaCl2 rightwards. In the K+ (22 mM)-depolarized isoproterenol (3.8×10-6 M)-treated atrial preparation, flurazepam (3×10-5 M) consistently suppressed contraction. Flurazepam (9×10-5 M) suppressed atrial contraction in tetrodotoxin (TTX) (2×10-5 M)-added normal Tyrode's solution, and CaCl2 (final: 8 mM) partially restored the contraction. These results suggest that flurazepam inhibits transmembrane Ca2+-influx into the atrial muscle cell.
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  • Takafumi NAGATOMO, Miyuki SASAKI, Hiroshi TSUCHIHASHI, Shoichi IMAI
    1983 Volume 33 Issue 4 Pages 851-857
    Published: 1983
    Released: November 07, 2006
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    Binding characteristics of the β-blockers and β-agonists with the β-adrenoceptors were investigated in 3H-dihydroalprenolol (3H-DHA) binding to rat heart membranes treated with neuraminidase. When 60% of the total sialic acid content in the membranes was removed, reproducibility of the binding assay became much better than was attainable without neuraminidase treatment, and the maximum density of β-adrenoceptors was increased. These data suggest that the binding of the test compounds with the β-adrenergic receptors in cardiac muscle was under the influence of the sialic acid of the glycocalyx of the membrane. The 3H-DHA binding sites in membranes treated with neuraminidase showed a strict stereo-specificity when tested with propranolol. The ranking order of inhibition of β-antagonists or agonists is: dl-propranolol > oxprenolol > alprenolol > pindolol > YM-09538 > labetalol > acebutolol > atenolol > metoprolol > sotalol > butoxamine > practolol as antagonists or l-isoproterenol > I-epinephrine > I-norepinephrine as agonists. A good correlation (r=0.91, P < 0.001) was observed between the K; values observed by the present binding assay and the pA2 observed in the guinea-pig atria relative to the positive inotropic effect by Bieth et al. (Br. J. Pharmacol. 68, 563-569, 1980), indicating that the present method will be useful for screening new β-adrenergic receptor antagonists or agonists.
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  • Itaru YAMAMOTO, Hitoshi OHMORI, Minoru SASANO
    1983 Volume 33 Issue 4 Pages 859-866
    Published: 1983
    Released: November 07, 2006
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    Keyhole lympet hemocyanin (KLH)-specific suppressor T (Ts) cells that suppress the in vitro secondary anti-trinitrophenyl (TNP) PFC response to TNP-KLH could be induced when murine spleen cells were precultured with KLH. N-(2-carboxy phenyl)-4-chloroanthranilic acid disodium salt (CCA) at 1-100 μg/ml augmented the in vitro induction of Ts cells when the cells were precultured with a suboptimal dose of KLH (10 μg/ml). Ts cell-induction was, however, rather slightly inhibited by the same concentrations of CCA when the lymphocytes were precultured with an optimal amount of KLH (100 μg/ml). In the in vivo experiments, the daily administration of 10 mg/kg CCA for 4 weeks augmented or inhibited Ts cell-induction when mice were immunized with a suboptimal (30 μg/body) or an optimal (100 μg/body) amount of KLH, respectively. However, CCA had no effect on the induction of Ts cells by concanavalin A in vivo. On the other hand, CCA augmented the induction of helper T (Th) cells both in vitro and in vivo when Th cells were induced with a suboptimal amount of antigens. In contrast, the augmentative effect was no longer observed when Th cells were induced by an optimal amount of antigens. These results suggest that CCA is a compound showing immunomodulating properties that affect Ts and Th cell-induction depending on immunological conditions. These immunopharmacological profiles are discussed in connection with its clinical application to an autoimmune disease like rheumatoid arthritis.
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  • Yoshimi KITADA, Tatsuo MIYAUCHI, Takashi KOSASA, Susumu SATOH
    1983 Volume 33 Issue 4 Pages 867-873
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    The present study was undertaken to examine whether the suppressing effect of intracerebroventricular (i.c.v.) administration of isoproterenol (ISO) on the immobility-reducing action of desipramine (DMI) in the forced swimming test was mediated through the presynaptic noradrenaline (NA) neurons and presynaptic α2-adrenoceptors in rat brain. As in the case of DMI, phenylephrine (i.c.v.) and yohimbine (i.p.) reduced the duration of immobility. The actions of DMI and yohimbine but not that of phenylephrine were diminished and potentiated by i.c.v. administration of ISO and atenolol, respectively. The suppressing effects of ISO were almost completely blocked by the pretreatment with atenolol. On the other hand, clonidine (s.c.) diminished the action of DMI as did ISO, although clonidine had no effect on the duration of immobility when given alone. The suppressing effect of clonidine was antagonized by the pretreatment with yohimbine at a dose which did not affect the duration of immobility, when given alone, nor influenced the action of DMI, whereas the effect of ISO was not affected by the same dose of yohimbine. These results suggest that the suppressing effect of ISO on the immobility-reducing action of DMI in the forced swimming test is mediated through the presynaptic NA neurons, and ISO acts through the presynaptic β1- but not α2-adrenoceptors.
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  • Hideo NAKAMURA, Chieko IMAZU, Katsumi ISHII, Yuichi YOKOYAMA, Toshiaki ...
    1983 Volume 33 Issue 4 Pages 875-883
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
    Zomepirac sodium inhibited the reflex hypertension caused by an injection of bradykinin into the splenic artery of anaesthetized dogs, but not that by injection of bradykinin plus PGE1. In the rat acetic acid writhing test, the potency ratio of intraperitoneal (ED50=0.41 μg/kg) to intravenous (ED50=33.5 μg/kg) anti-writhing activity of zomepirac sodium was 79.2 (37.1-173), though the ratio of codeine phosphate (373 μg/kg, i.p., 352 μg/kg, i.v.) was 0.934. When equipotent doses of zomepirac sodium were administered to rats receiving intraperitoneally acetic acid, the plasma zomepirac level after i.v. administration was more than 200 times that after i.p. administration, while the peritoneal exudate zomepirac contents were nearly equal after administration by both routes. Zomepirac sodium (5 μg/kg) did not produce significant anti-writhing activity after intracerebroventricular administration. From these results, it was suggested that zomepirac sodium produced analgesic action through a strong blockade of the hyperalgesia in the peripheral system.
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  • Takemi FUKUDA, Tatsumi TSUMAGARI
    1983 Volume 33 Issue 4 Pages 885-890
    Published: 1983
    Released: November 07, 2006
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    Effects of psychotropic drugs on the rage responses induced by electrical stimulation were investigated in cats with electrodes chronically implanted in the medial hypothalamus. Diazepam produced marked elevation in the threshold for directed attack and slight elevation in that for hissing. The inhibitory effect of etizolam on hissing was about 6 times as potent as that of diazepam. Anti-anxiety drugs such as diazepam, nitrazepam, lorazepam, clotiazepam and etizolam produced marked elevation in the directed attack threshold dose-dependently. The effect of chlorpromazine on directed attack was far less potent than that of anti-anxiety drugs. The anti-anxiety drugs used in this experiment had anti-pentetrazol activity in mice as well as muscle relaxant activity in cats. There were close correlations between the directed attack inhibition produced by the anti-anxiety drugs and both anti-pentetrazol activity and muscle relaxant activity. These results indicate that the above anti-anxiety drugs have a more potent inhibitory effect on the function of the medial hypothalamus than neuroleptic drugs. The inhibitory effect of anti-anxiety drugs on directed attack may be considered to correlate with clinical anti-anxiety effects.
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  • Makishige ASANO, Chiyoji OHKUBO, Kimio SAWANOBORI
    1983 Volume 33 Issue 4 Pages 891-893
    Published: 1983
    Released: November 07, 2006
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  • Fukiko UEDA, Norimoto URAKAWA
    1983 Volume 33 Issue 4 Pages 894-896
    Published: 1983
    Released: November 07, 2006
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  • Masao ENDOH
    1983 Volume 33 Issue 4 Pages 897-899
    Published: 1983
    Released: November 07, 2006
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  • Huei-Yann TSAI, Sadaaki MAEDA, Reizo INOKI
    1983 Volume 33 Issue 4 Pages 900-902
    Published: 1983
    Released: November 07, 2006
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  • Minoru SHIMODA, Takamitsu TSUBOI, Ei-ichi KOKUE, Toyoaki HAYAMA
    1983 Volume 33 Issue 4 Pages 903-905
    Published: 1983
    Released: November 07, 2006
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  • Ken-ichi SAITO, Masayoshi GOTO, Hideomi FUKUDA
    1983 Volume 33 Issue 4 Pages 906-909
    Published: 1983
    Released: November 07, 2006
    JOURNALS FREE ACCESS
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  • Koji TAKEUCHI, Youichi NOBUHARA, Susumu OKABE
    1983 Volume 33 Issue 4 Pages 910-914
    Published: 1983
    Released: November 07, 2006
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