The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 44, Issue 4
Displaying 1-21 of 21 articles from this issue
  • Lih Chu CHIOU, Suh Jeong HONG, Chuan Chiung CHANG
    1987 Volume 44 Issue 4 Pages 373-380
    Published: 1987
    Released on J-STAGE: September 15, 2006
    JOURNAL FREE ACCESS
    In order to elucidate the physiological role of endogenous adenosine in regulating the release of acetylcholine, the effects of 8-phenyltheophylline, an antagonist of adenosine receptors and dipyridamole, an uptake inhibitor of adenosine, on the contractile response and quantal release of acetylcholine during single and repetitive stimulations of isolated mouse phrenic nerve-diaphragm preparations were studied. The curves relating the concentration vs. inhibition of contractile response to added adenosine and ATP were shifted parallel to the left by dipyridamole, but were shifted to the right by 8-phenyltheophylline at concentrations with little Ca2+-mobilization or phosphodiesterase inhibition. In the absence of exogenously added adenosine, 8-phenyltheophylline increased the quantal content of end-plate potentials (1 Hz), whereas dipyridamole decreased the quantal content. Successive decrease of the amplitude of end-plate potentials (e.p.p. run-down) evoked at 50 Hz was not changed either by 8-phenyltheophylline or by dipyridamole, suggesting that adenosine or ATP released from the motor nerve does not accumulate to an effective concentration even after repetitive stimulation for a feed-back regulation of the transmitter release. It is concluded that endogenous adenosine does inhibit the release of acetylcholine from motor nerve. However, the source of adenosine may be mostly from the muscle and is probably not involved in the feedback autoregulation.
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  • Michio TERASAWA, Hiroshi MIKASHIMA, Tetsuya TAHARA, Yutaka MARUYAMA
    1987 Volume 44 Issue 4 Pages 381-386
    Published: 1987
    Released on J-STAGE: September 15, 2006
    JOURNAL FREE ACCESS
    The ability of etizolam, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3, 4-c]thieno[2, 3-e] [1, 4]diazepine (Y-7131), an anti-anxiety drug, to inhibit platelet-activating factor (PAF)-induced reactions was investigated in experimental animals in vivo. Etizolam (0.01-0.3 mg/kg, i.v.) dose dependently inhibited PAF (0.3 μg/kg, i.v.)-induced bronchoconstriction (Konzett and Rössler's method) in guinea pigs, but even at doses as large as 3 mg/kg, i.v., it had no effect on bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, angiotensin I or leukotriene D4. Etizolam (0.1-1 mg/kg, i.v.) also dose-dependently reversed PAF (1 μg/kg, i.v.)-induced hypotension in anesthetized rats. Injection of PAF into the tail veins of mice produced lethal shock within 10-30 min. Etizolam (0.1-3 mg/kg, i.v. and 1-10 mg/kg, p.o.) protected against the lethal effect of PAF (75 μg/kg, i.v.) in a dose-dependent manner. These results indicate that etizolam specifically inhibits the action of PAF in vivo.
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  • Hiroshi MIKASHIMA, Shuzo TAKEHARA, Yoshito MURAMOTO, Takako KHOMARU, M ...
    1987 Volume 44 Issue 4 Pages 387-391
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The antagonistic effect of etizolam, an anti-anxiety drug, on platelet-activating factor (PAF) was investigated in rabbit platelets in vitro. Etizolam inhibited PAF-induced aggregation in a dose-dependent manner, with an IC50 of 3.8 μM, about one tenth that of triazolam (IC50=30 μM). At 300 μM, it inhibited both ADP and arachidonic acid-induced aggregation only slightly, while the other anti-anxiety drugs tested had no effect on PAF-induced aggregation even at this concentration. Etizolam and triazolam inhibited the specific binding of 3H-PAF to PAF receptor sites on washed rabbit platelets with IC50 values of 22 nM and 320 nM, respectively. Diazepam and estazolam were inactive even at 1 μM. These results indicate that etizolam is a specific antagonist of PAF.
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  • Hisashi SATOH, Tomoyuki KUWAKI, Kiyoharu SHIRAKAWA, Yoshiro KOHJIMOTO, ...
    1987 Volume 44 Issue 4 Pages 393-403
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The effects of long-term dosing with tiapride for 21 days on barin dopamine receptors and dopamine turnover were compared with those of sulpiride and haloperidol. Haloperidol caused an increase in both antagonist (3H-spiperone) labeled receptors and agonist (3H-N, n-propylnorapomorphine) labeled ones, whereas tiapride acted on the agonist binding sites and sulpiride acted on the antagonist binding sites. The increases induced by sulpiride were only observed in the striatum, while those induced by tiapride and haloperidol were observed in both the striatum and limbic area. Dopamine and dopamine metabolites in the brain tissues were measured at 2 hr and 3 days after long-term dosing with the drugs as an indicator of dopamine turnover. They were higher at 2 hr and lower at 3 days than those of the saline treated controls, however, the increase at 2 hr was much less than that after single acute dosing with drugs. This suggested that all drugs induced tolerance with regard to dopamine turnover. In these studies, tiapride and sulpiride were less active than haloperidol in the effects on brain dopamine receptors and dopamine turnover. This generally weaker activity of sulpiride and tiapride suggest that the benzamide drugs have fewer side effects such as a tardive dyskinesia, than does haloperidol, even after long-term dosing. Furthermore, a slight difference between the effects of tiapride and sulpiride on the dopamine receptor subtypes in the brain subdivision was suggested.
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  • Hiroo HASHIMOTO, Kuniaki ISHII, Keisuke SATOH, Norio TAIRA
    1987 Volume 44 Issue 4 Pages 405-412
    Published: 1987
    Released on J-STAGE: September 15, 2006
    JOURNAL FREE ACCESS
    The present experiments were performed in anesthetized dogs in order to determine if DN-9693, a new antiplatelet agent known to selectively inhibit cyclic AMP phosphodiesterase (PDE), and isobutylmethylxanthine (IBMX), which inhibits both cyclic AMP and GMP PDEs, have different cardiovascular actions. With intra-arterial administration into the left anterior descending coronary, femoral, cranial mesenteric and renal arterial beds perfused at constant pressure with autologous blood, both agents increased blood flow in a similar dose range. DN-9693 was longer-acting than I BMX. Both agents were nearly equi effective in the femoral circulation, but DN-9693 was 1.5-2 times less effective than IBMX in the others. With intravenous administration, both agents were equi-effective in increasing the maximum rate of rise of left ventricular pressure, heart rate and myocardial oxygen consumption and in reducing mean blood pressure. However, DN-9693 was less effective in increasing coronary sinus outflow than IBMX. These results suggest the following: 1) Vasodilation in the somatic rather than the visceral circulation is important in reducing mean blood pressure. 2) Cyclic GMP may not be involved in the cardiac action of PDE-inhibitors. 3) Cyclic GMP may be involved in the vasodilator effect of PDE-inhibitors in the coronary, mesenteric and renal circulations but least involved in the femoral circulation.
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  • Tomihisa YOKOYAMA, Toshiharu KAMIOKA, Nobuyoshi IWATA, Takashi KOBAYAS ...
    1987 Volume 44 Issue 4 Pages 413-420
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The effects of RS-2232, a new antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain were investigated and compared with some clinically effective antidepressants. RS-2232 (3, 10 and 30 mg/kg, p.o.) increased the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) dose-dependently, 60 min after administration. Tyrosine (TYR) levels were not changed, but tryptophan (TRP) was significantly increased by 20% at 30 mg/kg of the compound. On the other hand, DA metabolites such as 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly reduced at all doses. 5-Hydroxy-indoleacetic acid (5-HIAA), a 5-HT metabolite, was decreased by 32% at 10 mg/kg. These changes caused by RS-2232 administration were similar to those of the classical inhibitor of monoamine oxidase (MAO), isocarboxazid (ISO), but rather different from those of imipramine (IMP) and mianserin (MIA). RS-2232 and ISO antagonized against reserpine (2 mg/kg, s.c.)-induced changes in the contents of monoamines and their metabolites. Furthermore, time-course experiments clearly showed that increase in the levels of monoamines by 10 mg/kg of RS-2232 was restored to the control levels within a few hours. These results suggest that RS-2232 has reversible MAO inhibiting properties in vivo in mouse brain.
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  • Tomihisa YOKOYAMA, Nobuyoshi IWATA, Takashi KOBAYASHI
    1987 Volume 44 Issue 4 Pages 421-427
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Effects of RS-2232 on monoamine oxidase (MAO) activities in mouse brain and liver were investigated with 5-hydroxytryptamine (5-HT), β-phenyl-ethylamine (PEA), and in some cases, kynuramine as substrate. IC50s of RS-2232 for 5-HT (100 μM) and PEA (20 μM) deaminations in brain mitochondrial preparations were 0.14 μM and 52 μM, respectively. RS-2232 was found to be a competitive inhibitor of 5-HT deamination in the preparation, and its Ki was 0.054 μM. The inhibitions of MAO in both brain and liver homogenate by RS-2232 in vitro measured with kynuramine (100 μM) were independent of the prolonged preincubation. 5-HT deaminations in the brain homogenates of mice treated with RS-2232 were decreased significantly by 15% and 59% at 10 and 30 mg/kg (p.o.) of the compound, respectively. On the other hand, PEA deaminations were not changed at the same doses. Pressor responses induced by intravenous tyramine (0.1-1.0 mg/kg) in anesthetized rats was little affected by oral administration of RS-2232 (3-30 mg/kg) once daily for two weeks. These results reveal that RS-2232 has a reversible and specific type-A MAO inhibiting property in mouse brain, and they suggest that RS-2232 is relatively safe in tyramine-potentiation.
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  • Takashi MATSUBARA, Akira TOUCHI, Noriko YAMADA
    1987 Volume 44 Issue 4 Pages 429-436
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Plasma concentrations of the major metabolites of 450191-S, a new sleep inducer which is a 1H-1, 2, 4-triazolyl benzophenone derivative, were determined in rats. Under the HPLC conditions employed, several major metabolites were detected in plasma, and thus the plasma concentration-time profiles for these metabolites were checked in rats in various states. When the animals were pretreated with high doses of 450191-S (200 or 600 mg/kg for 5 or 3 days, respectively) to induce hepatic drug-metabolizing enzymes, plasma concentrations of the metabolites after oral administration of a dose of 200 mg/kg of 450191-S decreased markedly depending on the induced enzyme activity. Pretreatment of rats with phenobarbital also caused decreased plasma levels of metabolites, which were almost the same as those in 450191-S-pretreatment. On the other hand, administration of beta-naphthoflavone to rats led to higher plasma levels of metabolites, and slower elimination compared with those in the control and 450191-S- or phenobarbital-pretreated rats. These results indicate that plasma levels of metabolites are regulated by the drug-metabolizing enzymes in the liver. It also suggests the participation of some specific forms of cytochrome P-450 in the biotransformation of 450191-S and its metabolites.
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  • Gozoh TSUJIMOTO, Keitaro HASHIMOTO
    1987 Volume 44 Issue 4 Pages 437-445
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    We have compared the vasopressor response of alpha-adrenoceptor agonists in young (2 month-old) and older (12 month-old) pithed rats both in the presence and absence of triiodo-L-thyronine (T3)-induced hyperthyroidism. There was no age-related changes in the pressor response to either the alpha1-selective agonist phenylephrine or the alpha2-selective agonists clonidine and UK-14, 304. However, T3-induced hyperthyroidism caused a selective reduction in postjunctional alpha2-adrenoceptor-mediated pressor responses but not alpha1-adrenoceptor-mediated ones in both age groups. In contrast to vascular alpha-adrenoceptors, there was an age-related decrease in the number of myocardial alpha1-adrenoceptor sites measured by specific binding of [3H]prazosin. With thyroid hormone treatment, the density of ventricular alpha, receptors was found to be further reduced even in the older rats. These results suggest that thyroid hormone and aging have different influences on the cardiovascular alpha-adrenoceptor system and that these two physiological variables are independently interrelated.
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  • Terumasa HASHIMOTO, Shigekatsu W. KOHNO, Katsuya OHATA, Yukiyoshi YANA ...
    1987 Volume 44 Issue 4 Pages 447-453
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    We investigated the influence of butyl 3-(1 H-tetrazol-5-yl) oxanilate (MTB) on the release of histamine and slow reacting substance of anaphylaxis (SRS-A) in vitro. MTB dose-dependently inhibited the release of not only histamine but also SRS-A from passively sensitized guinea-pig lung, while disodium cromoglycate (DSCG) hardly affected either release. MTB also resulted in a dose-dependent inhibition of the release of these mediators from the passively sensitized cynomolgus and rhesus monkey and that from human lung at concentrations similar to those inhibiting the release in the guinea-pig. Relatively lower inhibitory activities on the releases of both mediators from the cynomolgus monkey and human lung, but no effects on those from the rhesus monkey were observed with DSCG. MTB dose-dependently inhibited only SRS release from guinea-pig lung induced by phospholipase A2, although the compound did not show any inhibitory activity on the release of those from the calcium ionophore (A23187)-stimulated one. On the other hand, the release of SRS, but not that of histamine from the lung stimulated with A23187 as well as phospholipase A2 was inhibited by N-(3, 4-dimethoxycinnamoyl)-anthranilic acid (tranilast, N-5'). From these results, MTB was a potent inhibitor of the anaphylactic release of the mediators, particularly SRS-A. It was suggested that the inhibitory mechanism of MTB is different from those of DSCG and N-5'.
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  • Hajime IWABUCHI, Seiichi KOMORI, Hidenori OHASHI, Sadao KIMURA
    1987 Volume 44 Issue 4 Pages 455-459
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Previous studies have demonstrated that chicken rectum contains a peptide which exerts a potent, excitatory action on the smooth muscle of chicken rectum, and this peptide is most likely to be chicken neurotensin isolated recently from chicken small intestine. In the present study, the peptide was extracted from 2 kg of chicken rectums, and then it was isolated by gel filtration, ion exchange chromatography, high voltage paper electrophoresis and H PLC. Amino acid analysis of the peptide revealed that it is a tridecapeptide composed of aspartic acid (Asp), glutamic acid (Glu), proline (Pro), alanine (Ala), valine (Val), isoleucine (Ile), two residues of leucine (Leu), tyrosine (Tyr), histidine (His), lysine (Lys) and two residues of arginine (Arg). Its amino acid sequence was determined to be pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu-OH. The molecule is identical to chicken neurotensin.
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  • Tatsushi OKA, Akira TOUCHI, Takashi MATSUBARA
    1987 Volume 44 Issue 4 Pages 461-470
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Vitamin K-dependent gamma-glutamylcarboxylation activity in rat liver microsomes was monitored using the incorporation of 14CO2 into exogenous pentapeptide and endogenous protein substrates as indicators. Detergent solubilization of the microsomal enzymes was required for the activity to develop, but higher concentrations of detergent inhibited the enzymatic reaction. Pyridoxal-5'-phosphate (PAL-P) and dithiothreitol (DTT) stimulated the enzyme activity. The enzyme activity was observed when the hydroquinone form of vitamin K or the quinone form plus NADH was employed as the cosubstrate, but little activity was detected in the reaction system containing vitamin K-epoxide plus NADH plus DTT. N-Methyltetrazolethiol (NMTT), the substituent at the 3'-position of several beta-lactam antibiotics, inhibited the enzyme activity in vitro only in the reaction system containing NADH. Addition of DTT diminished the in vitro action of NMTT, while PAL-P and detergent did not affect it. The results indicate that the in vitro inhibitory action of NMTT is observable under some specific and restricted assay conditions. This paper also discusses the differences between the in vitro action and the in vivo effect of NMTT.
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  • Yoshiki MIURA, Tsugutaka ITO, Toshiaki KADOKAWA
    1987 Volume 44 Issue 4 Pages 471-479
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    To clarify the functional role of catecholamine in the septal area, we investigated the effects of dopamine (DA) and noradrenaline (NA) injected into the medial septum (MSN) on hippocampal synchronized theta wave activity (TWA) in immobilized rats. The injection of DA (1-4 μg) into the MSN dose-relatedly enhanced hippocampal TWA, i.e., an increase of the toral power in 3-7 Hz bands and little modification of the peak frequency. An enhancing effect of DA on TWA was also observed by the application into the diagonal band, but not into the lateral septum, nucleus accumbens, and lateral ventricle, indicating a selective effect of DA on the MSN and diagonal band. Furthermore, the enhancing effect of DA was blocked with the systemic treatment of haloperidol. Apomorphine (2 μg) injected into the MSN also increased the total power. NA (1-4 μg) enhanced TWA; however, NA, unlike DA, increased the peak frequency without modifying the total power, and the effect was not blocked by haloperidol, suggesting that the effect of NA on the septo-hippocampal neurons is different from that of DA. Muscimol (0.1 μg) and baclofen (0.05 μg) injected into the MSN depressed TWA, as indicated by a decrease of the total power. These results suggest that DA and NA, when injected into the MSN, heighten the functional level of the hippocampus.
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  • Sohta KATAYAMA, Akihiro NARIMATSU, Reiko SUZUKI, Toshihiko IIJIMA, Nor ...
    1987 Volume 44 Issue 4 Pages 481-488
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Effects of MCI-154, a newly synthetized cardiotonic drug with vasodilator property, on the membrane potential and currents of the isolated papillary muscles and the single ventricular cells of the guinea pig were examined. MCI-154 (10-7-10-4M) increased the developed tension in a dose-dependent manner without significant changes in the action potential configuration of the guinea pig papillary muscle. The slow response action potential obtained by increasing the extracellular K+ concentration to 24 mM was augmented by MCI-154 (10-6 and 10-4M). This effect of MCI-154 was not blocked by atenolol (10-6M). In voltage clamp experiments on single ventricular cells, the slow inward current was not affected, but the inward rectifier K+ current was reduced by higher concentration of MCI-154 (10-4M). Considering the “run down” phenomenon of the slow inward current, the possibility that MCI-154 might have a slight increasing effect on the slow inward current could not be ruled out. From these results, it can be concluded that the positive inotropic action of MCI-154 can be explained partially by the decrease in the inward rectifier K+ current, and probably by the increase in the Ca2+ sensitivity of the contractile protein system.
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  • Hiromichi TSURU, Sumiko NEGITA
    1987 Volume 44 Issue 4 Pages 489-492
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The buccal segment of the canine facial vein which was precontracted moderately with prostaglandin F relaxed to different extents in response to dopamine (DA), norepinephrine (NE), epinephrine (Epi) and isoproterenol (Isp). Propranolol (10-6M) reversed the relaxation responses to contractions. In the presence of an α-adrenoceptor blockade and inhibitors of neuronal and extraneuronal uptakes, the four catecholamines relaxed the vein fully, and the order of pD2 values was Isp (8.34) > Epi (7.53) ≅ NE (7.50) >> DA (5.31). The results indicate that in the canine facial vein, β-adrenoceptors predominate over α-adrenoceptors, and the subtype of β-adrenoceptor may be the β1-type.
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  • Akira OHTA, Akemichi BABA, Heitaroh IWATA
    1987 Volume 44 Issue 4 Pages 493-497
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The action of a new type of anti-anxiety compound, 5-{3-[4-(4-fluorophenyl)-1-piperazinyl]-propoxy}indan (BP-528), was tested on benzodiazepine receptor bindings and on [3H]-GABA release. BP-528 did not alter [3H]-diazepam binding to rat cerebral cortical and hippocampal membranes either in the presence or absence of GABA; and the binding of [3H]-propyl-β-carboline-3-carboxylate at low concentration (0.04 nM), which labels only the type I benzodiazepine receptor, was not changed by BP-528. BP-528 did not interact with the GABA-benzodiazepine receptor complex, which is related to the anti-anxiety activity of benzodiazepines. This compound affected neither GABA binding nor GABA uptake. Ten micromolar BP-528 depressed high K+-induced [3H]-GABA release from preloaded rat hippocampal slices. However, the same concentration of BP-528 also inhibited high K+-induced calcium uptake by rat cerebral cortical synaptosomes.
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  • Hiroo OGURA, Yoshiharu YAMANISHI, Kiyomi YAMATSU
    1987 Volume 44 Issue 4 Pages 498-501
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Ethylcholine aziridinium ion (AF64A), a putative cholinotoxin, was administered into the cerebroventricles of rats, and the effects on learning behaviors were observed. AF64A caused the impairment of learning acquisition in both passive and active avoidance responses. Physostigmine, a cholinesterase inhibitor, antagonized these changes at the doses of 0.03 to 0.1 mg/kg. Our behavioral study may indicate that the central cholinergic system might play a role in AF64A-induced impairment.
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  • Keizo SOGABE, Toshihiko UEMATSU, Hisakuni HASHIMOTO, Tohru OZAKI, Mits ...
    1987 Volume 44 Issue 4 Pages 502-505
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    The responsiveness to vasoactive agents in the perfused hindlimb of DOCA-salt hypertensive rats was examined and compared with that of normotensive rats. The vasoconstrictor responses in the femoral vascular bed to norepinephrine and serotonin were markedly potentiated in DOCA-salt hypertensive rats as compared with those in normotensive rats, and no change was found in the responses to angiotensin II. On the other hand, the vasodilatory response in DOCA-salt hypertensive rats to isoproterenol was attenuated without any marked changes in responsiveness to acetylcholine, nitroprusside and papaverine. These results suggested that the reduced vasodilator responses as well as the increased vasoconstrictor responses occur to some specific vasoactive agents in DOCA-salt hypertensive rats.
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  • Yoshinobu AKIMOTO, Kazuyoshi KURAHASHI, Hachiro USUI, Motohatsu FUJIWA ...
    1987 Volume 44 Issue 4 Pages 506-509
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    In isolated rabbit ear arteries incubated in a Ca2+-free medium with EGTA and nifedipine in the presence of norepinephrine, serotonin or histamine, an addition of Ca2+ induced a tonic contraction which is due to Ca2+ entry through receptor-operated Ca2+ channels (ROCs). Nitroglycerin (10-4 M) significantly inhibited the ROCs-dependent contractions produced by serotonin or histamine, but failed to inhibit the ROCs-dependent contraction by norepinephrine. These results suggest the possible existence of two types of receptor-operated Ca2+ channels in rabbit ear artery.
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  • Ikuko KIMURA, Masayasu KIMURA, Masaaki KIMURA
    1987 Volume 44 Issue 4 Pages 510-514
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Intracellular Ca2+ release in directly stimulated diaphragm muscles of mice was found to be dependent on external Ca2+, using the intracellular Ca2+ aequorin luminescence transient technique. The Ca2+ mobilization into the cells may operate via a voltage- and external Ca2+-dependent mechanism, and via a caffeine- and external Ca2+-independent one, from the Ca2+ pools in plasma membranes or in the terminal cisternae of sarcoplasmic reticulum.
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  • Naohisa ISHIKAWA, Akemi HAYAKAWA, Toshihiko UEMATSU, Mitsuyoshi NAKASH ...
    1987 Volume 44 Issue 4 Pages 515-518
    Published: 1987
    Released on J-STAGE: September 15, 2006
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    Effects of α-human natriuretic polypeptide (ANP) on isolated canine vascular strips were examined in 6 arteries and 5 veins. Under the preconstriction with either methoxamine, prostaglandin F or KCI, ANP relaxed the vascular strips to various degrees, depending on the region removed from the circulatory system. The largest relaxation was obtained in the pulmonary artery, suggesting that the pulmonary artery may be an important site of action of ANP.
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