The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 29, Issue 6
Displaying 1-16 of 16 articles from this issue
  • Yoshio SUZUKI, Mikio ITO, Yuji SUDO
    1979 Volume 29 Issue 6 Pages 821-828
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In order to elucidate the role of connective tissue components on the repair of ulcerated regions, quantitative changes in chemical components in ulcer tissue during the healing process were investigated in acetic acid-induced ulcer in rats. The ulcer index showed a peak on the 5th day after the operation, declined rapidly and maintained a slight level the 15th to the 60th days, without a complete recovery. In ulcer tissue, sialic acid and hexosamine remarkably increased in the early stages of healing, showing a peak on the 5th day. The patterns of time course of changes in both components ran almost parallel with those in the ulcer index. Uronic acid maintained slightly higher levels than normal levels the 5th to the 60th days. Hydroxyproline continued to increase with the time course from the 25th day. When acid mucopolysaccharides in ulcer tissue were isolated into various fractions, there were increases in hyaluronic acid on the 5th day, in chondroitin sulfate A and chondroitin sulfate C on the 30th day and chondroitin sulfate B on the 60th day, respectively. Significance of changes in these components in the healing process is discussed.
    Download PDF (437K)
  • Yoshio SUZUKI, Mikio ITO, Yuji SUDO
    1979 Volume 29 Issue 6 Pages 829-838
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    To elucidate mechanisms involved in the anti-ulcer action of cetraxate, the effects of this agent on the ulcer index (UI), fibrinolytic activity (FA) and contents of several connective tissue components in ulcer tissue were examined using aspirin- and acetic acid ulcers in rats. In aspirin ulcer. cetraxate (100 and 300 mg/kg p.o.), like tranexamic acid (500 mg/kg p.o.), ε-aminocaproic acid (500 mg/kg p.o.) and gefarnatc (200 mg/kg p.o.), inhibited both the UI and FA. However, aluminum sucrose sulfate (1000 mg/kg p.o.) was effective only against the UI and L-glutamine (500 mg/kg p.o.) failed to inhibit both parameters. In acetic acid ulcer, following oral, daily × either 5 or 8 administrations, cetraxate (200 and 300 mg/kg), gefarnate (200 mg/kg), aluminum sucrose sulfate (1000 mg/ kg) and L-glutamine (500 mg/kg) were effective on both the UI and FA. Tranexamic acid (500 mg/kg) and ε-aminocaproic acid (500 mg/kg) were ineffective on the UI, although both agents inhibited FA. In acetic acid ulcer, cetraxate induced increases in hexosamine and uronic acid, that is, acid rnucopolysaccharides (AMPS), especially chondroitin sulfate A and -C, whereas L-glutamine and aluminum sucrose sulfate resulted in increases in hexosamine and sialic acid, that is, glycoproteins. From these results, cetraxate may mainly accelerate the ulcer healing by increasing AMPS in ulcer tissue. Moreover, the local anti-FA property of this agent may be also beneficial in treating bleeding ulcers.
    Download PDF (604K)
  • Sumiko FUJINO, Takashi IGARASHI, Katsuji HOSHI
    1979 Volume 29 Issue 6 Pages 839-845
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The present study was performed to determine the effect of ouabain on Ca release from fragmented sarcoplasmic reticulum (FSR) isolated from cardiac muscles by changing the ionic environment and by caffeine. FSR was isolated from cat, guinea pig and frog cardiac muscles as microsomal fractions obtained biochemically, namely, by means of ultra-centrifugation at 8000 × g-35000 × g. After sufficient Ca2+-uptake by FSR in a potassium methan-sulfonate (KMS) medium, one ml of the suspension was passed through a Millipore filter. By this treatment, almost all FSR adhered to the filter. Three ml of potassium chloride washing medium was added to alter the ionic environment. One min later the washing medium was passed through the filter. A KMS washing medium containing 30 mM caffeine was used to induce the Ca release by caffeine. In the case of ouabain, the medium containing ouabain (2×10-6 M) was used. The time of ouabain treatment was 1 min. The grade of Ca release from FSR was almost the same among cat, guinea pig and frog cardiac FSR. Ouabain markedly potentiated Ca release from FSR by altering the ionic environment. These results suggest that the positive inotropic action of ouabain is dependent upon the potentiation of Ca release in SR vesicles of cardiac muscle.
    Download PDF (598K)
  • Yasuyuki NOMURA, Ikuko YOTSUMOTO, Tomio SEGAWA
    1979 Volume 29 Issue 6 Pages 847-854
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    To determine the functional significance of monoamines taken up into the newborn rat brain, a high K+-induced, Ca2+-dependent release of noradrenaline (NA), dopamine (DA) or serotonin (5-HT) from brain slices of the newborn rat was investigated and compared with that of the adult animal. Depolarization by increasing the potassium concentration in the medium induced the release of L-[3H]NA, [3H]DA or [3H]5-HT from brain slices prelabelled with the radioactive monoamines in the 2-day or 3-day-old rat as well as in the adult. The release of three [3H]amines was markedly inhibited by perfusing with Ca2+ free medium in the presence of EGTA (2.0 mM) at both newborn and adult stages, although the inhibitory potency of Ca2+ deficiency in the newborn preparation was lower than in the adult. The degree of the release against [3H]amines initially taken up in the newborn was of the same order of magnitude as those in the adult. It is suggested that NA, DA and 5-HT are stored in a functionally releasable pool of the nerve terminals of the central monoamine neurons in the rat and that these compounds act as neurotransmitters at birth and at the adult stage.
    Download PDF (454K)
  • Masao ENDOH
    1979 Volume 29 Issue 6 Pages 855-864
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    On the dog isolated right ventricular muscle, experiments were carried out in order to elucidate the characteristics of the cholinergic antagonism against the positive isotropic action (PIA) induced via different subcellular mechanisms. The relationship between cyclic AMP and cyclic GMP levels, and contractile force during cholinergic antagonism was assessed. Carbachol (10 μM) by itself decreased only slightly the tension developed, but inhibited prominently the PIAs of isoprenalinc, histamine, glucagon, theophylline and papaverine. The action of dibutyryl cyclic AMP was inhibited less than PIAs of other agents mentioned above. In contrast, carbachol did not affect the PIAs of calcium and g-strophanthin. The antagonism by carbachol of PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine was accompanied by a reduction of the intracellular cyclic AMP level elevated previously by these agents, and by an elevation of the intracellular cyclic GMP level. A good correlation was found between changes in the tension developed, and cyclic AMP and cyclic GMP levels during the cholinergic antagonism of PIAs induced by these agents in the dog ventricular myocardium.
    Download PDF (704K)
  • Takaharu ONO, Yukio MOTOYAMA, Shigeru SAKAI, Junko YONEDA, Shigenobu K ...
    1979 Volume 29 Issue 6 Pages 865-875
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of PGE2 and PGF on the tonus of isolated guinea-pig tracheal chain were investigated and compared with those of histamine and acetylcholine. PGE2 reduced tonus in normal resting state, but elevated tracheal tonus reduced by aspirin. Such PGE2-induced contractions did not exceed the initial resting tonus, and the magnitude and duration of the contractions progressively diminished with increase of PGE2 concentrations. Aspirin produced neither relaxation nor contraction in the presence of a low dose of PGE2. Unlike PGE2, PGF produced a dose-related contraction in the normal tracheal chain, and the contractile response to PGF was markedly potentiated by aspirin. In the presence of PGF, aspirin no longer produced tracheal relaxation but produced a dose-related contraction. The contractile effect of histamine but not of acetylcholine was also potentiated by aspirin, but there was a slight difference between PGF and histamine in that the potentiation of action of PGF by aspirin was more easily diminished by PGE2. These results suggest that PGE2 plays an important role in the maintenance of the resting tonus of the isolated guinea-pig tracheal chain, and in large doses it also acts as a tracheal relaxant and attenuates the tracheal responses to PGF and histamine.
    Download PDF (603K)
  • Mitsukazu KITADA, Kikue KUBOTA, Haruo KITAGAWA, Tetsuya KAMATAKI
    1979 Volume 29 Issue 6 Pages 877-887
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of addition of purified NADPH-cytochrome c (P-450) reductase on microsomal activities of aniline hydroxylation, p-phenetidine 0-deethylation and ethylmorphine and aminopyrine N-dernethylations were investigated utilizing microsomes from untreated, phenobarbital-treated and 3-methylcholanthrene-treated rats. The purified reductase was incorporated into microsomes. The drug oxidation activities were increased by the fortification of microsomes with the reductase while the extent of increase in the activities varied with the substrate and microsomes employed. The most pronounced enhancement was seen in p-phenetidine 0-deethylation, followed by aniline hydroxylation and aminopyrine and ethylmorphine N-demethylations. The enhancement was more remarkable in microsomes from rats treated with 3-methylcholanthrene or phenobarbital. α-Naphthotlavone inhibited p-phenetidine 0-deethylation activity markedly when the reductase was incorporated into microsomes, indicating that a larger amount of a species of cytochrome P-450 sensitive to the inhibitor was capable of participating in the oxidation of this substrate in the presence of the added reductase. One of the two Km values seen with higher concentrations of aniline or aminopyrine was altered by the fortification of microsomes with the purified NADPH cytochrome c (P-450) reductase. From these results, we propose that NADPH-cytochrome c (P-450) reductase transfers electrons to the selected one or two of multiple species of cytochrome P-450 more preferentially depending upon the substrate and the concentration of the substrate in microsomal membranes.
    Download PDF (698K)
  • Yasumichi HAGINO, Toshihiko UEMATSU, Masakatsu TACHIBANA
    1979 Volume 29 Issue 6 Pages 889-898
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The present study was designed to examine the properties of cyclic AMP-dependent protein kinase from normal and hypothyroid rat tissues. The activity of the liver enzyme decreased in hypothyroid rats and this reduced activity may be due to the decrease in synthesis of enzyme protein. The enzyme activity from the kidney of hypothyroid rats increased by 35% in the absence of cyclic AMP. Further, the enzyme from the kidney of hypothyroid animals responded to phenylephrine and isoproterenol. In the heart, the basal enzyme activity was the same in both groups, but the enzyme from the heart of hypothyroid animals did not respond to isoproterenol. When hypothyroid rats were treated with 3, 3', 5-triiodothyronine, the enzyme activities from those rat tissues showed essentially the same level as those of the corresponding normal ones. These results suggest that thyroid hormone regulates adrenergic agonists-mediated responses both at the sites of adrenoceptors and that of protein phosphorylation. Furthermore, the dependence on thyroid hormone varies according to the tissue.
    Download PDF (677K)
  • Jo MORI, Yoshihiko SATOH, Masaharu HASHIMOTO, Fumio HONDA
    1979 Volume 29 Issue 6 Pages 899-911
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA-blockers (haloperidol, sulpiride, and pimozide) and α-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, β-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic Juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion. Because DA- and α-blockers produced an increase in the accumulation of DA, dopaminergic and/or α-adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.
    Download PDF (1643K)
  • Jo MORI, Masaharu HASHIMOTO, Sueo MUKUMOTO, Fumio HONDA
    1979 Volume 29 Issue 6 Pages 913-921
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The metabolism of L-5HTP by the rat exocrine pancreas, and effects of blockers on the metabolism were studied by fluorescent histochemical and chemical methods. Histochemically. 5-hydroxytryptamine (5-HT) blockers (methyserigide and cyproheptadine) and dopamine (DA) blockers (haloperidol and sulpiride) produced no apparent changes in fluorescence pictures after injection of L-5HTP. α-blockers (phenoxybenzamine and phentolamine) and monoamine oxidase (MAO) inhibitor (iproniazide) produced an increased accumulation of 5-HT fluorescence in the apical regions of acinar cells where the zymogen granules are stored. Chemically, the 5-HT blockers decreased the 5-HT content after injection of L-5HTP. Sulpiride had no effect. Haloperidol decreased the 5-HT content. MAO inhibitor resulted in a vast accumulation of 5-HT. Some differences were noted between the L-5HTP metabolism and that of L-dopa: e.g. (I) L-5HTP was more slowly eliminated, and (2) 5-HT blockers produced a decreased content of 5-HT after injection of L-5HTP, in contrast to the finding that DA-blockers produced an increased content of DA after injection of L-dopa. The mechanism responsible for the differences is discussed in relation to the possible pharmacological effects of L-5HTP and L-dopa on the secretion from the exocrine pancreas of rats.
    Download PDF (1338K)
  • Jo MORI, Hisashi SATOH, Yoshihiko SATOH, Fumio HONDA
    1979 Volume 29 Issue 6 Pages 923-933
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of L-dopa, L-5HTP, a few amines, and related compounds on the pancreatic rate of flow, protein secretion, and bicarbonate secretion were studied in conscious rats. Single injections of L-dopa, DA and apomorphine did not modify the rate of flow, while an increase was seen with infusion of DA. L-dopa stimulated the protein secretion. L-5HTP and 5-HT decreased the rate of flow and protein secretion. Effects of L-dopa and L-5HTP on the protein secretion were prevented by DA- and 5-HT blockers, respectively. Neither L-dopa nor L-5HTP had any effect on the bicarbonate secretion. Secretin and cholinergic agents (acetylcholine and carbamylcholine) strongly stimulated the rate of flow of pancreatic juice. α-Agonists (phenylephrine and clonidine) decreased the rate of flow, and the effects were inhibited by an α-blocker. The α-agonists had no effect on protein secretion. Although, α-blockers (phenoxybenzamine and phentolamine) had no effects on the rate of flow, they did decrease the protein secretion. Isoproterenol was a potent secretagogue, and the effect was suppressed by a β-blocker. Histamine had no effect on the rate of flow. The results were discussed in relation to our previous histochemical and chemical findings, and the species difference between rats and dogs in response to the amines.
    Download PDF (660K)
  • Koichi NAKAYAMA, Takeshi OSHIMA, Hiroyuki KOIKE
    1979 Volume 29 Issue 6 Pages 935-945
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    -The β-blocking, antiarrhythmic, and local anesthetic effects of the racemic mixture and optical isomers of bucumolol, 5-methyl-8-(2-hydroxy-3-t-butylamino-propoxy) coumarin hydrochloride, were studied in dogs, guinea-pigs and frogs. In blocking the positive chronotropic response to isoproterenol, the levo-isomer of bucumolol was about 40 times more potent in dogs, and 270 times in guinea-pigs than its dextro-isomer and twice as effective in both species as the racemic mixture. In frog sciatic nerves bucumolol was 1/10-1115 as potent in local anesthetic action as propranolol on a weight basis. Dextro- and levo-isomers and racemic bucumolol neither elevated electrical threshold for propagated impulses nor prolonged the effective refractory period of the dog right atrium. The levo-isomer and racemic bucumolol were capable of suppressing aconitine-induced atrial arrhythmia, while the dextro-isomer was less effective Both isomers and racemic bucumolol were capable of reversing ventricular arrhythmia caused by ouabain, but the effective dose of the levo-isomer was significantly less than that of the dextro-isomer. The results suggest that both specific β-blocking activity and non-specific membrane action of bucumolol suppressed experimental arrhythmias in dogs produced by aconitine and ouabain.
    Download PDF (720K)
  • Motoki KOBAYASHI, Tadahiro SHIKIMI, Sadao MIYATA, Katsuya OHATA
    1979 Volume 29 Issue 6 Pages 947-950
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Download PDF (260K)
  • Ryoichi ISHITANI, Akira KARASAWA, Katsumi MIZUSAKI, Takio IWAMOTO
    1979 Volume 29 Issue 6 Pages 950-953
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Download PDF (257K)
  • Hitoshi ITO, Hiroyoshi HIDAKA, Mamoru SUGIURA
    1979 Volume 29 Issue 6 Pages 953-957
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Download PDF (344K)
  • Kazuhiko IWATSUKI
    1979 Volume 29 Issue 6 Pages 957-959
    Published: 1979
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Download PDF (172K)
feedback
Top