The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 37, Issue 3
Displaying 1-12 of 12 articles from this issue
  • Jyunji YAMAMOTO
    1985 Volume 37 Issue 3 Pages 227-234
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The EEG power spectra of the motor cortex (MC) and hippocampus (HPC) in rabbits were characterized, and the effects of CNS acting drugs on the spectra were investigated. The EEGs of rabbits with chronically implanted electrodes were recorded with bipolar leads and simultaneously analyzed for 15 min with a computer to obtain their power spectra. MC spectra had one peak of delta wave, and HPC spectra had two peaks of delta and theta waves, whose peak powers and frequencies were changed in correspondence to the level of consciousness. Pentobarbital (20 mg/kg, i.v.) produced the peaks at 11 and 4 Hz in MC and HPC spectra, respectively. Morphine (5 mg/kg, i.v.) produced the peak at 7 Hz in MC spectra and shifted the theta wave peak of HPC to lower frequencies. Diazepam (4 mg/kg, i.v.) produced the peak at 14 Hz in MC spectra and decreased the two peak powers in HPC spectra. Chlorpromazine (4 mg/kg, i.v.) shifted the theta wave peak of HPC to lower frequencies. Amitriptyline (5 mg/kg, i.v.) increased the peak powers of the delta waves in MC and HPC spectra. These results suggest that each of the five CNS acting drugs produces the characteristic spectra, and they are different from the spectra obtained during normal behavioral states.
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  • Shigehiko NARUMI, Yasuo NAGAI, Mitsuru KAKIHANA, Naoki YAMAZAKI, Akino ...
    1985 Volume 37 Issue 3 Pages 235-244
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effects of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-2619) on the contents, turnover, release and uptake of monoamines, especially serotonin (5-HT), in various brain regions of Wistar rats were studied in vivo and in vitro. In normal rats, an intraperitoneal (i.p.) dose of 100 mg/kg of CV-2619 had no significant effect on the levels of norepinephrine (NE), dopamine (DA) and their metabolites, and 5-HT in the brain regions examined, but it increased the levels of 5-hydroxyl ndole-3-acetic acid (5-HIAA), the main metabolite of 5-HT, in many brain regions. In rats with cerebral ischemia, a low dose (10 mg/kg, i.p.) of CV-2619 normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-HT biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.), decreased the levels of 5-HT in all brain regions to one-third of the control levels 24 hr after administration in normal rats. CV-2619 (10, 30 or 100 mg/kg, i.p.), administered 24 hr after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreases in the hippocampus, diencephalon and brain stem in a dose-dependent manner. In vitro CV-2619, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of the hippocampus and diencephalon. CV-2619 slightly inhibited and PCA markedly inhibited 5-HT uptake into hippocampal slices. The mechanism of the 5-HT releasing action of CV-2619 in hippocampal slices seems to be mediated through endogenous calcium. These results suggest that CV-2619 has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon and brain stem of rats.
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  • Seiyu SUGIYAMA, Takashi IGARASHI, Koichi UENO, Tetsuo SATOH, Haruo KIT ...
    1985 Volume 37 Issue 3 Pages 245-252
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    -O-Ethyl O-p-nitrophenyl phenylphosphonothioate (EPN)-induced inhibition of rat liver microsomal carboxylesterase (CEase) and formation of O-ethyl O-p-nitrophenyl phenylphosphonate (EPNoxon), an oxygen analog of EPN, were enhanced remarkably by addition of NAD in vitro. This potentiation of the anti-CEase action of EPN by NAD was significantly inhibited by addition of SKF 525-A or potassium thiocyanate (KSCN); and a simultaneous decrease in cytochrome P-450 contents was also observed. Addition of N-ethylmaleimide (NEM) at various concentrations inhibited potentiation of the anti-CEase action of EPN by NAD in parallel with inhibition of liver microsomall dehydrogenase activities. In conclusion, NAD was enzymatically reduced to NADH, a cofactor of microsomal dehydrogenase(s), and then formation of EPNoxon through microsomal cytochrome P-450-coupled monooxygenase was accelerated. Consequently, inhibition of CEase by EPN was potentiated.
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  • Teruo NAKADATE, Eriko AIZU, Satoshi YAMAMOTO, Hirota FUJIKI, Takashi S ...
    1985 Volume 37 Issue 3 Pages 253-258
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Teleocidin (5 μg/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 μmol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 μmol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 μmol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 μmol/mouse), nordihydroguaiaretic acid (NDGA) (30 μmol/mouse), quercetin (10 μmol/mouse), and 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoqu1none (AA861) (10 μmol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 μmol/mouse) and quercetin (10 μmol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.
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  • Yoshio SAKODA, Masahide MUNEMURA, Yoshihiro FURUKI, Yasuyuki HATADA, M ...
    1985 Volume 37 Issue 3 Pages 259-267
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The presence of Ca2+ in the incubation medium was required for stimulation of the release of the immunoreactive β-endorphin-like peptide (IR-β-EP) from the dispersed cells of the neurointermediate lobe of rat pituitary gland by adenosine 3', 5'-monophosphate (cAMP) analogs, a phosphodiesterase inhibitor, L-isoproterenol, cholera toxin and forskolin. The basal release observed in the absence of the stimulants was also dependent on the addition of Ca2+. A calcium antagonist (verapamil) inhibited the effects of the stimulants. A calcium ionophore (A23187) enhanced the release of IR-β-EP, but did not stimulate the formation of cAMP. These findings suggest that Ca2+ has the essential role in the release of β-endorphin from the neurointermediate lobe of rat pituitary gland.
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  • Tetsu HAYASHI, Sakutaro TADOKORO
    1985 Volume 37 Issue 3 Pages 269-276
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Male neonates of Wistar strain rats were given 0.63-2.50 g/kg/day of ethanol, i.p., for 7 successive days from day 6 to 12 after birth. The acquisition processes of the discriminated lever-press avoidance response (intertrial interval: 25 sec, warning stimuli presentation: 5 sec, foot shock intensity: 110V, 0.5 mA, 50 Hz, AC) were investigated for 20 separate sessions from day 60 after birth. The preference test for ethanol was done beginning at 120 days of age. No significant differences in body weights were detected between saline and ethanol-pretreated groups. However, learning retardation was observed in all groups pretreated with ethanol. In these groups, slow responses to warning stimuli followed by escape responses from shocks delivered were often observed in early training sessions. An enhanced preference for ethanol was observed in all groups pretreated with ethanol for 7 successive days at maturity. These results suggest the possibility that learning ability and preference for ethanol in adult rats are strongly influenced by pretreatments with ethanol during the early postnatal period.
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  • Eiichiro OKABE, Haruo KOHNO, Yasushi KATO, Chisato ODAJIMA, Haruo ITO
    1985 Volume 37 Issue 3 Pages 277-283
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effect of pH on the excitation-contraction coupling system of canine masseter muscle was studied by evaluating the functional integrity of the sarcoplasmic reticulum (SR) and myofibrils. Increasing proton concentration (pH 7.0-5.8) significantly reduced oxalate supported SR calcium uptake velocity, while Ca2+-stimulated, Mg2+-dependent ATPase activity was unaffected by pH. The efficiency ratio of calcium transport, or the coupling ratio (μmoles Ca2+ transported/μmoles ATP hydrolyzed), decreased from 1.094±0.042 at pH 7.0 to 0.946 ±0.036 at pH 6.0 (P<0.05) and to 0.780±0.024 at pH 5.8 (P<0.01). Myofibrillar pCa (-log [free Ca2+])-ATPase activity was unaffected between pH 7.0 and pH 6.5. At pH 6.0, increasing Ca2+ concentration inhibited myofibrillar ATPase activity, and this inhibitory phenomenon was accentuated at pH 5.8. Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km at low pH. It is concluded that acidosis significantly uncouples calcium transport from ATP hydrolysis in the SR of masseter muscle and significantly alters myofibrillar ATPase activity. It is hypothesized that these defects may explain an observed depression in skeletal muscle cell function during ischemia.
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  • Akira KARASAWA, Kazuhiro KUBO, Katsuichi SHUTO, Nobuhiro NAKAMIZO
    1985 Volume 37 Issue 3 Pages 285-291
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The interaction of 5-hydroxytryptamine (5HT) and ketanserin was investigated in isolated rat vas deferens. Ketanserin (10-7 M) almost completely abolished the phasic and the following rhythmic contractions induced by 5HT, whereas the inhibition by prazosin (10-6 M) or methysergide (10-6 M) of 5HT-induced contractions were incomplete. The amplitude of twitch contractions of vas deferens subjected to low frequency (0.1 Hz) field stimulation were substantially unchanged by 5HT (10-7-10-5 M) per se. After pretreatment of the tissue with ketanserin (10-8-10-6 M), 5HT, in a concentration-dependent manner, attenuated the amplitude of twitch contractions. Such attenuation of the amplitude was not observed after pretreatments with methysergide (10-8-10-6 M) or prazosin (10-7-10-5 M). The 5HT-induced inhibition of twitch contractions in the presence of ketanserin was not antagonized by phentolamine, propranolol, methysergide, morphine, promethazine, cimetidine, atropine or indomethacin. It is suggested that 5HT has dual (excitatory and inhibitory) effects upon nerve transmission of rat vas deferens, and only the excitatory effect is suppressed by ketanserin.
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  • Kyozo YAMANAKA, Shigeru KIGOSHI, Ikunobu MURAMATSU
    1985 Volume 37 Issue 3 Pages 293-295
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Using rat cerebral cortex membranes, the inhibitory effect of DG-5128 against (3H)-clonidine binding was compared between low (α2L) (in the presence of EDTA) and high (α2H) affinity states (in the presence of excess magnesium) of alpha2-adrenoceptor for agonists. The Ki value (pKi=6.79) of DG-5128 in the α2L state was 6.4 times higher than the value in the α2H state. Thus, DG-5128 produces alpha2-adrenoceptor antagonism through the selective interaction with an α2L state of the receptor.
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  • Krishnaswami RAMABADRAN
    1985 Volume 37 Issue 3 Pages 296-299
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effects of Mr2096, Mr2097, diprenorphine, (-)bremazocine and Mr2266 on jumping latencies were evaluated in Swiss, CXBK, C57BL, CXBH and CBA strains of mice. Mr2096 and Mr2097 respectively produced analgesia and hyperalgesia in these strains of mice. Thus their effects on nociception were mediated by stereoselective opioid receptors. Diprenorphine also produced hyperalgesia which might be mediated by both mu and kappa receptors. Kappa receptors also appeared to mediate hyperalgesia at least in Swiss and CBA strains, as both (-)bremazocine and Mr2266 shortened the jumping latencies.
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  • Yoshihiro KIYOTA, Kazuhiro HAMAJO, Masaomi MIYAMOTO, Akinobu NAGAOKA
    1985 Volume 37 Issue 3 Pages 300-302
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effect of idebenone (CV-2619) on memory impairment was studied in rats with cerebral embolization. The cerebral embolization, produced by injecting 2000 microspheres into the internal carotid artery, caused a significant impairment in passive avoidance response. Repeated administrations of idebenone (30 mg/kg/day, i.p.), partially but significantly improved the impairment of the passive avoidance response in the embolized rats. The results suggest that the repeated administration of idebenone exerts an ameliorating effect on memory impairment induced by cerebral embolization.
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  • Masato IKEDA, Hiroshi MIYAZAKI, Akira MATSUSHITA
    1985 Volume 37 Issue 3 Pages 303-305
    Published: 1985
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Simultaneous measurements of electrochemical and electrophysiological changes in the substantia nigra pars compacta of the rat were tried with a single carbon fiber microelectrode. Electrochemical detection of catecholamines was done by differential pulse voltammetry. The effects of haloperidol on the level of catecholamines in extracellular spaces and on dopaminergic neuronal discharges were investigated. Haloperidol induced an increase in unitary discharges parallel to the elevation of the catecholamine level. With this technique, direct information can be obtained on the relationship between released catecholamines and unitary neuronal activity.
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