The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 32, Issue 4
Displaying 1-21 of 21 articles from this issue
  • Toshiaki NAKASHIMA, Tatsuro TANIKO, Kinya KURIYAMA
    1982 Volume 32 Issue 4 Pages 583-589
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    To determine the therapeutic efficacy of taurine administration on liver injury, the effect of taurine on hepatic lipid peroxide level following carbon tetrachloride (CCl4) administration was investigated. To CCl4 intoxicated rats (CCl4, 2 ml/kg, i.p.), 3 ml of a 10% aqueous solution of taurine was administered after CCl4 administration (at 12, 16, and 20hr after), and rats were sacrificed at 24 hr after CCl4 administration in order to estimate the level of lipid peroxides in the liver. The decrease of hepatic lipid peroxidation induced by CCl4 was noticed in the taurine-treated rats. Taurine had no effect on mixed function oxidase activity in hepatic microsomes as well as no effect on hepatic antioxidant content in the CCl4-intoxicated rats. Hepatic taurine content decreased significantly 12 and 24 hr after CCl4 administration, whereas oral administration of taurine to CCl4-intoxicated rats was able to protect these rats from hepatic taurine depletion. These results suggest that hepatic taurine may play a critical role on the protection of hepatocytes against hepatotoxins such as CCl4 and the administration of taurine may be useful in the treatment of hepatotoxininduced liver injury.
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  • Akinobu NAGAOKA, Mitsuru KAKIHANA
    1982 Volume 32 Issue 4 Pages 591-597
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    In stroke-prone spontaneously hypertensive rats (SHRSP), urinary excretion of sodium and water and glomerular filtration rate (GFR) are markedly decreased by acute normalization of the renal perfusion pressure using an aortic clamping technique. To examine the mechanism for the decreased sodium and water excretion, SHRSP rats were subjected to bilateral renal denervation. Sodium and water excretion and GFR in SHRSP with aortic clamping were significantly restored by the renal denervation. The restoration was more prominent in the urine flow and GFR. When renal perfusion pressure was normalized by administration of sympatholytic drugs in another group of SHRSP, sodium and water excretion were decreased. However, the extent of the decrease in urine flow but not in sodium excretion was significantly less than that in SHRSP with aortic constriction. GFR was not changed by administration of the sympatholytic drugs. Renal denervation lowered the blood pressure in SHRSP. These results suggest that renal sympathetic nerve activity is greatly involved in the reduced water excretion and partly involved in the reduced sodium excretion in SHRSP rats.
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  • Yasumitsu YAMANAKA, Toru EGASHIRA
    1982 Volume 32 Issue 4 Pages 599-606
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effects of ethanol on the contents of norepinephrine (NE) and dopamine (DA) and the activities of related enzymes in the various regions of rat brains with different doses and mode of administration of ethanol were investigated. In acute ethanol intoxication, steady-state levels of NE were not altered. Continuous ethanol intoxication, however, significantly reduced NE contents and tended to decrease the activity of dopamine-β-hydroxylase in the hippocampus. The decrease in NE contents became more significant during ethanol withdrawal, especially in the medulla oblongata and the striatum. DA contents were increased in the brain-stem region in all ethanol-treated rats. The increase in DA contents correlated with the increase in tyrosine hydroxylase activity. The present data suggest that the dopaminergic system may contribute to the development of physical dependence on ethanol.
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  • Arata GOTO, Minoru WATANABE
    1982 Volume 32 Issue 4 Pages 607-614
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effect of 4-aminopyridine (4-AP) on the isolated superior cervical ganglion of the rat was investigated by means of the sucrose-gap-method. 4-AP initiated discharges of postganglionic neurons and simultaneously increased the amplitude of the compound action potential evoked by supramaximal preganglionic nerve stimulation at concentrations higher than 0.1 mM. Ganglionic discharges induced by 4-AP were characterized by low frequency and high amplitude. These 4-AP-induced discharges were unaffected by removal of the preganglionic nerve trunk. These discharges were suppressed by d-tubocurarine, Ca removal from saline, or preganglionic denervation, whereas discharges of high frequency and low amplitude were observed after 4-AP in Ca-free solution or in denervated preparations. During perfusion with 4-AP, antidromic action potentials were recorded from the preganglionic nerve. When 4-AP was applied to the preganglionic nerve trunk, however, postganglionic responses were unaffected. It is suggested that discharges of postganglionic neurons were induced by 4-AP, possibly as a result of an initiation of action potentials in preganglionic terminal fibres running in the ganglion.
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  • Yoshio SUZUKI, Masahisa ASANO, Hiroyoshi HIDAKA
    1982 Volume 32 Issue 4 Pages 615-624
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effects of W-7, W-5, No. 233, and chlorpromazine on sympathetic nerve transmitter efflux were compared in superfused canine basilar arterial preparations preloaded with [3H] -norepinephrine. In vitro experiments suggest that these agents are selective calmodulin antagonists. The electrical transmural stimulation-induced efflux of tritium was reduced by W-7 and W-5, although they were unexpectedly equipotent since W-5 is a chloride-deficient derivative of W-7 and has a lower affinity for calmodulin than does W-7. The median inhibitory concentration (IC50) of W-7 for stimulation-induced efflux was 3.4×10-6 M. The addition of No. 233 at relatively high concentrations (3×10-5 M and 5×10-5 M) caused a reduction in stimulation-induced efflux. Chlorpromazine produced a dual effect on the efflux: enhancement at low concentrations (below l×10-6 M) and reduction at high concentrations. The IC50 values of No. 233 and chlorpromazine were 3.5×10-5 M and 2.5×10-5 M, respectively. The additions of these four agents also caused a significant elevation in the spontaneous basal efflux of tritium from the preparations. The concentrations of the agents that elevated the spontaneous efflux to the level of half the stimulationinduced efflux were closely fitted to the IC50 values for stimulation-induced efflux. This finding indicates that the elevation in spontaneous efflux is directly proportional to the reduction in electrical stimulation-induced efflux. From these findings, it is concluded that naphthalenesulfonamides including W-7 have a direct effect on sympathetic nerve terminals which is independent of the effect on calmodulin.
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  • Fukio KONNO, Issei TAKAYANAGI
    1982 Volume 32 Issue 4 Pages 625-632
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effects of morphine on calcium uptake into synaptosomes isolated from acutely or chronically morphine-tolerant rat brain was studied. Addition of morphine inhibited the depolarization-stimulated uptake of calcium without affecting uptake under nondepolarizing conditions. This inhibition was prevented by simultaneous addition of naloxone with morphine before calcium uptake was initiated. Acute tolerance to morphine increased depolarization-stimulated synaptosomal calcium uptake. On the other hand, chronic exposure of rats to morphine to elicit tolerance to and physical dependence on morphine did not influence synaptosomal calcium uptake. However, these preparations apparently lost the ability of in vitro morphineinhibition of calcium uptake into the synaptosomes. Our results suggested that adaptive changes of synaptosomal calcium uptake produced by exposure to morphine may be involved in tolerance and physical dependence development, but influence of morphine on calcium uptake by the synaptosomes isolated from the rats acutely tolerance to morphine was differed from that of chronic tolerant rats.
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  • Mamoru TERADA, Akira I. ISHII, Hideto KINO, Motohito SANO
    1982 Volume 32 Issue 4 Pages 633-642
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effects of various cholinergic agents on the motility of Angiostrongylus cantonensis were studied to define the neuropharmacological properties of this worm. Stimulation of the motility and/or contraction were shown by eserine, ACh, carbachol, nicotine, DMPP, pyrantel, and Ba2+, but not by pilocarpine and McN-A-343. Contraction was similarly observed by these agents in the preparations paralyzed with praziquantel. Paralysis was caused remarkably by d-tubocurarine and slightly by succinylcholine, while the contraction induced by eserine and DMPP was little influenced by these drugs. Both the motility and the eserine-induced contraction were little influenced by hexamethonium, but stimulated remarkably by atropine. Though hemicholinium-3, morphine, and picrate showed little effect, guanidine stimulated remarkably the motility and also the eserine-induced contraction. The stimulatory action of guanidine was antagonized by strychnine. Strychnine paralyzed the motility, and the eserine-induced contraction was antagonized by the pre and post-treatment with strychnine. From these results, it is suggested that the excitatory cholinergic mechanism in A. cantonensis is nicotinic, and it is basically similar to that reported in Ascaris suum.
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  • Mamoru TERADA, Akira I. ISHII, Hideto KINO, Motohito SANO
    1982 Volume 32 Issue 4 Pages 643-653
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effects of some possible neurotransmitters such as GABA, adrenergic drugs, and 5-HT and their antagonists on the motility of Angiostrongylus cantonensis were studied. Paralysis was caused by GABA, avermectin Bia (Av-Bia), piperazine and α-adrenergic agonists such as adrenaline, noradrenaline, phenylephrine, clonidine and methoxamine, but not by β-adrenergic agonists such as isoproterenol. The paralysis by GABA or Av-Bia was antagonized by GABA antagonists such as picrotoxin and/or bicuculline with cholinergic agents such as N-methylcytisine (N-MC) or eserine. The paralysis elicited by α-adrenergic agonists was antagonized by α-adrenergic antagonists such as phentolamine and dibenamine, but not by β-adrenergic antagonists such as propranolol. 5-HT affected the motility of A. cantonensis paralytically or spastically. The paralysis induced by 5-HT was antagonized by α-adrenergic antagonists such as phentolamine and dibenamine, while the contraction induced by this compound was further stimulated by N-MC, but antagonized by strychnine. Other agents such as glutamine, glycine, aspartic acid, taurine, and substance P showed little effect on the motility of A. cantonensis. From these findings on the neuropharmacological properties of A. cantonensis, it is suggested that this worm is useful as an excellent nematodal model for the investigation of anthelminthics. In addition, this worm may also useful as one of screening models of drugs affecting the central nervous system in mammals.
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  • Haruo KOBAYASHI, Akira YUYAMA, Yoshiaki TOKONABE, Naonori MATSUSAKA
    1982 Volume 32 Issue 4 Pages 655-663
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effects of thiol compounds on methylmercury chloride (MMC)-inhibited choline acetyltransferase (ChAT) activity and MMCinhibited high affinity choline uptake of rat brain tissue were studied in vitro. D-penicillamine (D-Pc) and dimercaptosuccinic acid (DMS) reversed the MMC-inhibited ChAT activity dose-dependently. Equilibrium dialysis of MMC-inhibited ChAT against the buffer containing 10-3M D-Pc reversed the ChAT activity almost completely. The reversal effect of D-Pc (monothiol compound) on MMC-inhibited ChAT was significantly more potent than that of DMS (dithiol compound). D-Pc and DMS almost equally reversed the MMC-inhibited high affinity choline uptake by synaptosomes in a dose dependent fashion. Washing with a solution containing D-Pc or DMS equally reversed the MMC-inhibited high affinity choline uptake in a dosedependent fashion. Neither D-Pc nor DMS could reverse the hemicholinium-3-inhibited high affinity choline uptake.
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  • Toichi TAKENAKA, Iwaki MIYAZAKI, Masaharu ASANO, Saburo HIGUCHI, Hiroo ...
    1982 Volume 32 Issue 4 Pages 665-670
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Vasodilator and hypotensive effects of (+) and (-) nicardipine were investigated in anesthetized dogs. When administered intravenously, (+) nicardipine was 3 times as potent as the (-) isomer in increasing vertebral blood flow and in lowering mean blood pressure. When injected into the vertebral artery, (+) nicardipine was also 3 times as potent as the (-) isomer in increasing vertebral blood flow. Upon both routes of administration, the duration of the action after (+) nicardipine was longer than that after the (-) isomer. However, there were no differences of plasma nicardipine levels after intravenous injection of both isomers to conscious beagle dogs. The LD50 values of (+) nicardipine in mice and rats upon intravenous injection were only 1.5-2 times smaller than those of the (-) isomer. These results indicate that there exists a stereoselectivity of vasodilator and hypotensive actions among the nicardipine isomers.
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  • Hiroshi HIGUCHI, Kunio TAKEYASU, Yasuhiro WATANABE, Shuji UCHIDA, Hiro ...
    1982 Volume 32 Issue 4 Pages 671-678
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Studies were made on developmental changes in phasic contractions of isolated rat vas deferens in response to norepinephrine (NE) and acetylcholine (ACh), which are mediated by α-adrenergic and muscarinic cholinergic receptors (α-R and m-R). The ED50 values of both contractions were almost constant during development, but the maximum responses to NE and ACh per wet weight and the relative contractions by NE and ACh to that by 100 mM K+ decreased greatly between 3 and 8 weeks after birth. However, the α- and m-receptors, assayed by measuring binding of [3H]-WB4101 and [3H]-quinuclidinyl benzylate (QNB), increased quantitatively per g wet weight and per mg protein between 2 and 8 weeks after birth, but did not change qualitatively. Thus, a discrepancy between the increases of α- and m-receptors and decreases of the maximum responses to NE and ACh was found, and possible mechanisms for this are discussed.
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  • Yasuo OHNO, Toru KAWANISHI, Atsushi TAKAHASHI, Yutaka KASUYA, Yoshihit ...
    1982 Volume 32 Issue 4 Pages 679-688
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Using a spectrophotometer connected to a microcomputer, the carbon monoxide difference spectrum of renal microsomal dithionitereduced cytochrome P-450 was measured avoiding the effects of the contaminating mitochondrial cytochromes and hemoglobin by subtracting the CO difference spectrum of a succinate-treated microsomal suspension from that of a dithionite-treated one. By this method, we quantitatively determined the microsomal cytochrome P-450 in kidneys from various species. The absorption peak of the renal microsomal cytochrome P-450 was about 452 nm in rats and about 450 nm in mice, hamsters, rabbits, guinea pigs, dogs, and pigs. Compared with the renal cytochrome P-450 contents in rats, the contents on a g tissue basis were greater in pigs, dogs, and mice and were about the same in hamsters and rabbits. The renal cytochrome P-450 contents in guinea pigs were less than those in rats.
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  • Mitsuji AGATA, Hiroshi GOTO, Yoshihiro TSURIYA, Koichi TACHIBANA, Tosh ...
    1982 Volume 32 Issue 4 Pages 689-697
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    A newly synthesized compound, [[3-(1H-tetrazol-5-yl)-phenyl] amino]oxoacetic acid n-butyl ester (MTB) has been demonstrated to be an orally active antiallergic agent. This compound inhibited the 48-hr passive cutaneous anaphylaxis (48-hr PCA) induced by IgE in rats. In guinea pigs, MTB also inhibited the 8-day passive cutaneous anaphylaxis (8-day PCA) and the 8-day passive systemic anaphylaxis induced by IgE. The compound partially inhibited the IgG-mediated 3-hr PCA in rats and guinea pigs, but failed to have any effect on the rabbit IgG-mediated 3-hr PCA in these animals. In the rat, MTB was not an antagonist of histamine or serotonin. The antiallergic effect of MTB was not mediated via any adrenergic mechanisms. MTB significantly inhibited histamine release from rat peritoneal cells induced by rat IgE in vitro.
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  • Ken-ichi SASAKI, Shinobu FURUSAWA, Giichi TAKAYANAGI
    1982 Volume 32 Issue 4 Pages 699-707
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Effects of doxapram, a respiratory stimulant, on the action of other drugs and the activity of the hepatic drug-metabolizing enzyme were studied in mice. The hypothermic effect induced by aminopyrine and the muscle relaxative effect induced by meprobamate were potentiated by the pretreatment with doxapram 60 min before. Furthermore, doxapram significantly enhanced the lethalities of picrotoxin and strychnine and the analgesic actions of aminopyrine and morphine. The plasma concentration of aminopyrine or pentobarbital in doxapram-treated mice was higher than those in untreated mice, and the plasma concentration of normustard related to an active metabolite of cyclophosphamide after the administration of cyclophosphamide was lower in doxapram-treated mice. On the other hand, doxapram (50 mg/kg, i.p.) reduced remarkably the activities of aminopyrine N-demethylase and aniline hydroxylase in the hepatic 9, 000×g supernatant fraction, and also reduced the cytochrome P-450 contents in hepatic microsomes. However, no significant alteration by doxapram was observed on the activities of NADH-ferricyanide reductase and NADPH-cytochrome c reductase and cytochrome b5 contents. It seems likely that the mechanisms of the interaction between doxapram and combined drugs involved the depression of the hepatic drug-metabolizing system in microsomes and a subsequent variation of drug level in the plasma.
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  • Yoko UCHIDA, Teruko NOMOTO
    1982 Volume 32 Issue 4 Pages 709-718
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The effect of intracerebroventricular administration of chlorpromazine (CPZ) on the serum level of free fatty acid (FFA) was studied in rats. Injection of CPZ into the lateral ventricle caused a transient decrease in serum FFA, showing the lowest level after 30 min. This decrease in serum FFA caused by CPZ was significantly inhibited by simultaneous injection of dopamine or apomorphine, although noradrenaline and serotonin had no effect. The dopaminergic blocking agent haloperidol caused a rapid decrease in serum FFA. After central chemical sympathectomy with the intracerebroventricular injection of 6-hydroxydopamine, the response to CPZ of serum FFA was completely abolished; but after peripheral sympathectomy by i.v. injection of 6-hydroxydopamine, a partial inhibition of the action of CPZ was shown. These results suggest a possible involvement of the central dopaminergic mechanism in the decrease in serum FFA after intracerebroventricular injection of CPZ.
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  • Hideyo OHSHIKA, Haruo TAKEMURA, Junichiro ENDO, Mamoru TANAKA
    1982 Volume 32 Issue 4 Pages 719-726
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    The authors previously reported that low doses of labetalol potentiated isoproterenol (ISO)-induced salivation in mice. The present study was carried out to ascertain the potentiating effect of labetalol in in vitro experiments using rat parotid tissue slices and their isolated cells. ISO-induced amylase release was enhanced by low concentrations of labetalol (less than 10-6 M), while it was inhibited by high doses (more than 10-5 M). This potentiating effect of labetalol did not occur in the Ca-free medium used for incubation or in experiments using the dispersed parotid cells or the parotid tissues which were obtained from 6-hydroxydopamine or reserpine-treated rats. The effect of ISO on cyclic AMP accumulation in parotid tissue was completely blocked by the addition of labetalol in concentrations which were sufficient to increase the ISOinduced amylase release. Labetalol also inhibited the ISO-induced reduction of potassium release in parotid tissue. From these results, it is concluded that increases in the secretion of amylase and potassium from salivary glands due to the stimulation of glandular α-adrenoceptors by endogenous norepinephrine may play an important role in the potentiating effect of labetalol on ISO-induced salivation in mice.
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  • Hideaki KARAKI, Tadahiko SUZUKI, Norimoto URAKAWA, Yukisato ISHIDA, Sh ...
    1982 Volume 32 Issue 4 Pages 727-733
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    In guinea pig taenia coli, added 45.4 mM K+ induced a sustained contraction, increased the rate of oxygen consumption, and slightly decreased the ATP content. In substituted 154.2 mM K+, Na+-deficient solution, only a transient contraction was induced. Oxygen consumption also showed only a transient increase and ATP content of the muscle rapidly decreased. Such an inhibition of sustained contraction and the decrease in both oxygen consumption and ATP content were recovered when 5.5 mM pyruvate or 50 mM NaCl was added during the 154.2 mM K+-induced contraction. In rabbit aorta, substituted 80 mM K+, 74.2 mM Na+ solution induced a sustained contraction, increase in oxygen consumption, and no change in ATP content. The 80 mM K+ solution without added glucose also induced a sustained contraction followed by a slight increase in oxygen consumption and a slight decrease in ATP content. The 154.2 mM K+, Na+-deficient solution produced similar changes in both oxygen consumption and ATP content as the 80 mM K+, glucose depleted solution. However, the 154.2 mM K+ solution induced only a transient contraction in the vascular smooth muscle. When 100 mM sucrose was hyperosmotically added to the 154.2 mM K+ solution, the suppressed muscle tension increased again, although the ATP content did not increase. From these and the previous results, it is concluded that glucose utilization by the taenia coli is inhibited in the 154.2 mM K+, Na+-deficient solution, and the decreased energy production of the muscle cell does not compensate the increased energy consumption induced by the high concentration of K+. In the aorta, although the Na+-deficient solution also decreases ATP production, it is the cell swelling induced by a high KCl concentration in the medium, not the decrease in energy metabolism, that has a direct inhibitory effect on muscle tension.
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  • Kazuhiko IWATSUKI, Fujio IIJIMA, Shigetoshi CHIBA
    1982 Volume 32 Issue 4 Pages 735-737
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
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  • Hiroaki HISA, Susumu SATOH
    1982 Volume 32 Issue 4 Pages 738-741
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
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  • Yukio HASEGAWA, Takushi X. WATANABE, Koichiro KAWASHIMA, Hirofumi SOKA ...
    1982 Volume 32 Issue 4 Pages 742-745
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
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  • Misako NAMIMA, Koichi OKAMOTO, Yutaka SAKAI
    1982 Volume 32 Issue 4 Pages 746-749
    Published: 1982
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
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