The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 27, Issue 5
Displaying 1-19 of 19 articles from this issue
  • Mitsukazu KITADA, Kan CHIBA, Tetsuya KAMATAKI, Haruo KITAGAWA
    1977 Volume 27 Issue 5 Pages 601-608
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21 mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in inhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.
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  • Jaromir KOMAREK, Christoph MANSFELD
    1977 Volume 27 Issue 5 Pages 609-620
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Activity of Carnigen on the cardiovascular system, following intraduodenal and intravenous application, was investigated in normotone and hypotone dogs anaesthetized with sodium pentobarbital, 35-40 mg/kg intraperitoneally. Intraduodenal application of 1 and 3 mg Carnigen/kg caused an increase in blood pressure and tachycardia. The total peripheral resistance was lessened, in normotone as well as hypotone dogs, whereas the cardiac output and stroke volume were augmented. A rise in myocardial inotropy and cardiac work in combination with a moderate increase in left ventricular 02 consumption also occurred as result of the action of Carnigen. An increase in the central and peripheral venous pressure was registered during continuous infusion of Carnigen. Coronary flow was also raised, in a dose dependent manner within the range of 0.1 to 1 mg Carnigen/kg i.v. The rise in arterial blood pressure is due to an increase in cardiac output, resulting from the positive inotropic action of this compound on the myocardium. The reduction in arterial resistance can be explained on the basis of a possible interaction between the inosine, released from Carnigen, and the adenosine already present in the system.
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  • Mayuki FUJIWARA, Kinya KURIYAMA
    1977 Volume 27 Issue 5 Pages 621-627
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of continuous oral administration of PCB (polychlorobiphenyls, 10-100 mg/kg/day, 4 weeks) on tissue levels of L-ascorbic acid (vitamin C), pyridoxal phosphate and riboflavin (vitamin B2) in various organs and on hepatic metabolism of L-ascorbic acid were examined in male Wistar rats weighing 150-250g. Riboflavin contents in the liver, kidney, brain, heart and testis were not altered by PCB treatments, whereas the hepatic level of pyridoxal phosphate, a biologically active form of vitamin B6, was significantly reduced by PCB administration. Under the same experimental conditions, L-ascorbic acid contents in the liver, kidney, lung and testis showed a significant increase. Histochemical studies revealed that in the adrenal gland, increase of L-ascorbic acid was localized in the fasciculate and reticular zones of cortex, respectively. It was found that increase of L-ascorbic acid in the liver is caused predominantly by activation of biosynthesis at the steps of galactose to D-glucuronic acid and is not due to changes in the catabolic processes of L-ascorbic acid per se. Possible significance of these changes in tissue levels and/or metabolism of vitamins in the occurrence of PCB intoxication is briefly discussed.
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  • Masaru SORIMACHI
    1977 Volume 27 Issue 5 Pages 629-634
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of postsynaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-, β-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life.
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  • Shingo YANO, Masuo AKAHANE, Masatoshi HARADA
    1977 Volume 27 Issue 5 Pages 635-643
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Exposure of the rat to restraint and water immersion stress enhanced a characteristic gastric movement in a 2 to 4-hr latent period. The mechanism of producing such gastric movement was studied in connection with changes in the sympatho-adrenal activity. Acute bilateral adrenalectomy and reserpine pretreatment significantly hastened occurrence of the gastric movement and guanethidine pretreatment showed a similar tendency. Epinephrine content in the adrenals of the stressed group markedly decreased at the time of occurrence of the gastric movement. Urinary excretion of epinephrine and norepinephrine continued to increase for 3 hr and for 6 hr respectively, after the onset of stress, and both excretory rates declined thereafter. Epinephrine and norepinephrine were much more effective on depressing the stressinduced gastric movement than cortisone and ACTH. It was suggested that: 1) at the initial stage of stress, the adrenal function as well as the sympathetic nervous function was activated, and a large amount of epinephrine and norepinephrine was secreted, which brought about an inhibition of the gastric movement; 2) at the subsequent stage, the parasympathetic nervous function became more prominent than the sympathoadrenal one and initiated the gastric movement; and 3) contribution of corticosteroids and/or ACTH to the gastric movement was small, if any.
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  • Masako MORIKAWA, Michiko INOUE, Minoru TSUBOI
    1977 Volume 27 Issue 5 Pages 645-651
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Esterase activity, and contents of protein, phospholipid, and cholesterol were measured in the liver and intestinal mucosa of male rats after 24 hr of food deprivation or treatment with corn oil (2.5 ml/kg, 3 days), aspirin (500 mg/kg, 3 days), cinchopen (600 mg/kg, 3 days), or phenobarbital (100 mg/kg, 3 days). After food deprivation for 24 hr, the total esterase activity was decreased in the intestinal mucosa and liver. Treatment with corn oil, increased the mucosal esterase activity to about twice that of the control but hepatic esterase activity did not change markedly, while total activity was decreased in post-mitochondrial supernatant or microsomal fraction of intestinal mucosa by treatment with cinchophen. Total and specific activities were increased in lysosomal fraction of intestinal mucosa by treatment with aspirin or cinchophen. In these rats, hepatic esterase activity was not markedly changed. In rats treated with corn oil or phenobarbital, cholesterol content in the intestinal mucosa was decreased, and the phospholipid content was increased significantly. By food deprivation or treatment with cinchophen, the content of protein, phospholipid or cholesterol decreased. These results indicate that characteristics of the esterase activity of intestinal mucosa are quite different from that in the liver. The dietary factor and drug adininstration may interfere with the intestinal ester-hydrolysis capacity.
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  • Mitsukazu KITADA, Tetsuya KAMATAKI, Haruo KITAGAWA
    1977 Volume 27 Issue 5 Pages 653-657
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The addition of EDTA to the incubation mixture containing rabbit liver microsomes and ferrous ion resulted in 2-fold increase of lipid peroxidation activity. Such an enhancement was not observed in rat liver microsomes. The maximum lipid peroxidation activity seen in rabbit microsomes in the presence of EDTA and ferrous ion was about 80% that seen in rat liver microsomes. From these results, it is likely that low lipid peroxidation activity in rabbit liver microsomes may account for the insufficiency of an EDTA-like factor(s) in rabbit liver microsomes.
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  • Eiichi HAYASHI, Shizuo YAMADA, Motokuni MORI
    1977 Volume 27 Issue 5 Pages 659-665
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The mechanism of anti-nicotinic actions of hexamethonium, mecamylarnine and adenosine was investigated in guinea pig isolated ileum. Mecamylamine shifted the dose-response curves for nicotine to the right with a gradual depression. On the other hand, hexamethonium shifted the curves to the right without a depression and adenosine made only a gradual depression, suggesting the different modes of their antinicotinic actions. The transmurally-stimulated twitch response was unaffected, partially inhibited and abolished by hexamethonium, mecamylamine and adenosine, respectively. These three compounds also had little effect on direct muscle response to acetylcholine and on the acetylcholinesterase activity of the ileum. From these results, it is suggested that the antagonism to the effect of nicotine shown by mecamylamine does not appear to he a simple competitive blockade of ganglionic receptors as is the case with hexamethonium and that adenosine may antagonize the effect of nicotine non-competitively. The mechanism by which mecamylamine and adenosine showed anti-nicotinic action is discussed.
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  • Tsutomu NOHNO, Yasuko HAYASHI, Yoshimichi MURAYAMA
    1977 Volume 27 Issue 5 Pages 667-678
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Experiments were carried out in an attempt to elucidate the mechanism of fasting-induced natriuresis in conscious rats. Female animals were given a low sodium diet and saline in a fixed concentration for at least three days, and deprived of food thereafter. The sodium balance significantly shifted to negative independently of potassium supply in intact rats. Such was also observed in the dexamethasone-replaced, adrenalectomized rats and was not affected by further administration of aldosterone. In addition, the diuretic effect of insulin in fasted intact rats was not evident in the fed diabetic rats in which diabetes had been induced by streptozotocin. Such findings suggested participation of factors other than insulin. The natriuresis of fasting in intact rats appears to involve two factors, one of which is independent of the sodium intake level. Dependence on the sodium intake level may be derived from alteration of the solute diuresis-like effect of drinking saline when animals are fasted. These results suggest that neither aldosterone nor insulin is a major causal factor involved in fasting-induced natriuresis.
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  • Isao YAMAGUCHI, Yoshiaki AKIMOTO, Hiromichi NAKAJIMA, Akio KIYOMOTO
    1977 Volume 27 Issue 5 Pages 679-687
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effect of diltiazem on glucose-induced insulin secretion was investigated in the rat islets of Langerhans isolated by a collagenase digestion technique. It was found that B-cells, main constituents of isolated islet preparations, had a well-preserved ultrastructural appearance immediately following isolation or after incubation with glucose or glucose and diltiazem. The islets released a large amount of insulin upon stimulation with glucose and CaCl2. Diltiazem (10-6-10-4 M) produced a doserelated inhibition of glucose-induced insulin secretion and this effect was antagonized by the increase in extracellular concentration of CaCl2. The inhibitory effect of diltiazem on the insulin secretion was also counteracted by dibutyryl-3', 5'-cyclic AMP or by theophylline. Among calcium-antagonists tested, nifedipine produced the most powerful inhibitory action on the insulin secretion, while the effect of verapamil was similar to or somewhat stronger than that of diltiazem. It was suggested that diltiazem may reduce the intracellular concentration of free calcium ion, thus causing an inhibitory effect on the glucose-induced insulin secretion by the isolated islets of Langerhans.
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  • Minoru HIRATA, Katsuyoshi KAWAZOE, Masao TANABE, Kenzo KIKUCHI
    1977 Volume 27 Issue 5 Pages 689-700
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In dogs, intracoronary doses of CV-1674, adenosine (ADS) and 2-Cl-ADS for doubling coronary flow were estimated as 5.0, 2.0 and 0.4 μg/dog, and i.v. doses 31, 71 and 2.5 μg/kg, respectively. ADS and 2-Cl-ADS decreased, while CV-1674 increased LV dp/dt. Intravenous infusion (30 min) of CV-1674 (10 μg/kg per min) and ADS (700 μg/kg per min) decreased coronary resistance to approximately the same extent. Decreases in blood pressure, total peripheral resistance and myocardial O2 consumption with ADS were more prominent than those with CV-1674. ADS produced a marked bradycardia that was not evident with CV-1674. Neither agent had a significant influence on myocardial efficiency. In guinea pig atria, ADS and 2-Cl-ADS exerted negative effects while those with CV-1674 were positive inotropic and chronotropic. In cats, intraduodenal ADS (10 mg/kg) produced no effects on cardiohemodynamic parameters. CV-1674 (250 and 500 μg/kg) increased myocardial tissue blood flow (MBF) with a slight hypotension in a dose-dependent manner, whereas 2-Cl-ADS (100, 250 and 500 μg/kg) increased MBF only with the highest dose concomitantly with marked hypotension and bradycardia. These results suggest that CV-1674 induces selective coronary vasodilation with less depression on cardiohemodynamics, and is relatively well absorbed from the intestinal tract. The pharmacological profile of the compound, therefore, differs from that of ADS and 2-Cl-ADS.
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  • Takashi MATSUBARA, Akira TOUCHI
    1977 Volume 27 Issue 5 Pages 701-708
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Cyanidc, an inhibitor of many hemoproteins, was shown to affect a number of microsomal drug-metabolizing activities catalyzed by cytochrome P-450. The N-demethylation reaction of aminopyrine was inhibited noncompetitively by this inhibitor in microsomal preparations from rats. The binding reaction of aminopyrine with microsomal cytochrome P-450 was also modified by cyanide, and an abnormal aminopyrine-induced difference spectrum of microsomes appeared when cyanide was added to the reaction mixture. Partial dissociation of cytochrome P-450-cyanide complex by aminopyrine was observed by spectrophotometrical and epr spectroscopic methods. These results suggest that aminopyrine and cyanide reciprocally affect binding with cytochrome P-450 and modification by cyanide of aminopyrine binding reaction with the hemoprotein produces an inhibition of N-demethylase activity.
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  • Keisuke TAKEDA, Yumi KATANO, Yoshito NAKAGAWA, Tokumasa TSUKADA, Mikio ...
    1977 Volume 27 Issue 5 Pages 709-720
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of aminophylline, proxyphylline and a proxyphylline-Melilotus extract-rutin-mixture (theoesberiven) on the heart and coronary circulation were studied in the canine heart-lung preparation supported by a donor in comparison with those of isoproterenol (Isp). All the three methylxanthines produced an increase in the coronary flow associated with a definite positive inotropic effect. In contrast to the effects of Isp, increase in the heart rate was minimal with these compounds. Myocardial redox potential (ΔEh) changed to more negative values, although the changes were smaller than that produced by Isp. Since it was found that these substances produced a disproportionately greater increase in the coronary flow as compared with an increase in the myocardial oxygen consumption, the effects of these substances on the myocardial high-energy phosphate compounds were also studied in the isolated perfused heart preparation of the guinea pig. All the three compounds produced a reduction of the creatine phosphate (Cr-P)/(Cr-P+Inorganic phosphate) ratio and the energy charge of the adenylate system, in the following order, aminophylline>proxyphylline=theoesberiven. Antagonism towards adenosine was found with the three methylxanthines used. In the isolated left atrial preparation of the guinea-pig, aminophylline induced a definite potentiation of the positive inotropic effect of isoproterenol, while the potentiation produced by proxyphylline and theoesberiven was minimal.
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  • Shigeo MURAI, Yasumi OGURA
    1977 Volume 27 Issue 5 Pages 721-726
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effect of erabutoxin (ETX) was examined on respiration of rabbits. A single dose of 15 μg/kg or 25 μg/kg of ETX did not cause respiratory paralysis, but repeated administration of 15 μg/kg of ETX at 3 hour intervals (three times) or 25 μg/kg at 4 hour intervals (twice) caused fatal respiratory paralysis. Furthermore, a single administration of 50 μg/kg of ETX caused fatal respiratory paralysis within 2 hours after the administration in all animals. This respiratory paralysis caused by ETX was reversible and of long duration (10-20 hour). This respiratory paralysis was not blocked by the administration of anticurare agents (neostigmine, edrophonium) or respiratory stimulants (nikethamide, picrotoxin, dimorpholamine). Since ETX had no influence on the circulatory system, death caused by ETX was prevented with application of artificial respiration.
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  • Shigetoshi CHIBA
    1977 Volume 27 Issue 5 Pages 727-734
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Inotropic and chronotropic effects of 5-hydroxytryptamine (5-HT) were investigated in twenty-five isolated canine atrial preparations and three isolated paced ventricular preparations which were suspended in the bath and perfused with arterial blood from the carotid artery of the heparinized support dog. 5-HT was administered into the cannulated sinus node artery in a dose range of I to 300 μg. In small doses of 1 to 3 μg, 5-HT induced a negative chronotropic and inotropic response. At relatively higher doses over 10 μg, 5-HT induced a biphasic response: a slight negative chronotropic and inotropic response, followed by a long-lasting positive response. With large doses, only a positive chronotropic and inotropic response was induced in the majority of cases. Even in the ventricular preparations, 5-HT produced a similar response pattern in inotropism. 5-HT-induced positive chronotropic and inotropic responses were completely inhibited by pretreatment with an adrenergic beta-blocking agent, propranolol, or a non-depressant beta-blocking agent, carteolol, and desipramine, but were not influenced by tetrodotoxin treatment. After the treatment with carteolol or despramine, 5-HT-induced negative responses were potentiated. 5-HT-induced negative chronotropic and inotropic responses were not inhibited by methysergide and atropine. From these results, it is suggested that 5-HT induces a direct negative chronotropic and inotropic response and an indirect positive response via its tyramine-like action.
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  • Shigetoshi SUZUKI, Tetsuo SATOH, Mikio YAMAZAKI
    1977 Volume 27 Issue 5 Pages 735-744
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The absorption and tissue distribution of ochratoxin A (OCT A) following a single oral dose of OCT A were investigated in adult, male Wistar rats. In experiments concerning excretory patterns of OCT A, 14C-OCT A was used. A relatively large amount of OCT A was found in the circulating blood 48 hours after dosing. The patterns of absorption, tissue distribution and excretion of OCT A were affected by acute catarrhal enteritis produced by OCT A and/or ochratoxin a (OCT α). Quantitative data show that OCT A is distributed mostly in the kidney and this finding is closely associated with the tissue specifity of OCT A-induced nephrotoxicity. OCT A was found to be hydrolyzed to its major metabolite, OCT α by addition of the homogenate of pancreas, duodenum and ileum. Approximately 56% of OCT A administered was excreted in both urine and feces as the unchanged toxin and OCT α during 120 hours following dosing. A relatively larger amount of OCT α was detected as compared with that of OCT A.
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  • Yoshimi MISU, Teruko HOSOTANI, Emiko NAKASHIMA, Hiroaki NISHIO
    1977 Volume 27 Issue 5 Pages 745-748
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Motohiko UEDA, Saburo MATSUDA
    1977 Volume 27 Issue 5 Pages 748-751
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Saizo YANAURA, Tsutomu SUZUKI
    1977 Volume 27 Issue 5 Pages 751-753
    Published: 1977
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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