The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
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Volume 28, Issue 4
Displaying 1-20 of 20 articles from this issue
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  • RELATIONSHIP BETWEEN SERUM GASTRIN LEVELS AND GASTRIC SECRETION IN HEIDENHAIN POUCH DOGS
    Hiroko FUKE, Isamu YAMAGUCHI, Jun HIROI, Shigenobu KUMADA
    1978 Volume 28 Issue 4 Pages 511-520
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.511
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    Relationship between serum gastrin levels and gastric secretion was studied in Heidenhain pouch dogs. Bethanecol and tetramethylammonium increased gastric secretion without any significant change in the serum immunoreactive gastrin (IRG) level. Histamine increased gastric secretion but decreased the serum IRG level. Tetragastrin evoked gastric secretion concomitantly with an elevation of the serum IRG level, and the relationship was significant. Food-intake promptly increased the serum IRG level which correlated with the increased gastric secretion. Except for the first 15-min value after food-intake, a better correlation was obtained and was almost the same as that with tetragastrin-stimulation. Hexamethonium reduced the food-induced secretion rate in parallel with reduction of the serum IRG level. Correlation between the secretion rate and serum IRG level after dosing was almost the same as that of the control. Atropine and secretin induced a stronger inhibition on the secretion rate than on the serum IRG level. Prostaglandin E/reduced the secretion rate, but produced no inhibitory effect on the serum IRG level. These results suggest that the food-induced gastric secretion in Heidenhain pouch dogs is due to the action of endogenous gastrin, and that hexamethonium and prostaglandin E1 affect respectively the gastrin and parietal cells. Atropine and secretin affect both parietal and gastrin cells.
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  • RELATIONSHIP BETWEEN GASTRIC SECRETION AND SERUM GASTRIN LEVELS IN DOGS ANESTHETIZED WITH MORPHINE AND URETHANE
    Isamu YAMAGUCHI, Hiroko FUKE, Michiko TSUJITA, Shigenobu KUMADA
    1978 Volume 28 Issue 4 Pages 521-526
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.521
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    The serum levels of immunoreactive gastrin (IRG) and secretion of gastric juice were simultaneously determined in dogs anesthetized with morphine and urethane. There was a significant positive linear correlation between secretion and serum IRG level in these dogs. Serum IRG level and gastric secretion were reduced by bilateral vagotomy at the neck. The amount of gastric juice was reduced dose-dependently by an intravenous injection of atropine (0.001-0.016 mg/kg), hexamethoniurn (0.064-1 mg/kg) and secretin (2-8 U/kg). The reduction of gastric secretion paralleled that of the serum IRG level. However, the reduction of gastric secretion did not parallel that of serum IRG level under the influence of prostaglandin E1 (0.002-0.008 mg/kg i.v.) and duodenal acidification. Prostaglandin E1 and duodenal acidification reduced gastric secretion without the reducing serum IRG level. These findings were discussed in relation to the mechanism of gastric juice stimulation by morphine, and it is suggested that endogenous gastrin release through the vagal and non-vagal pathways participates in morphine-induced gastric secretion. The difference in inhibitory effect between duodenal acidification and secretin suggests the possibility that substances other than secretin may participate in the regulation of gastric secretion in dogs.
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  • CONTRACTILE RESPONSES OF ISOLATED DOG MESENTERIC ARTERIES TO ANGIOTENSIN I, II AND III
    Noboru TODA, Shigehiro HAYASHI, Mizuo MIYAZAKI
    1978 Volume 28 Issue 4 Pages 527-534
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.527
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    The addition of angiotensin (Ang-) I, II and III caused a dose-dependent contraction of helically cut strips of dog mesenteric arteries. Tachyphylaxis developed following repeated additions of angiotensins. Average median effective concentrations of Ang-I, II and III were 3.7, 0.8 and 2.5×10-8 M, respectively. Contractile responses to the angiotensins were attenuated to a similar extent by Ang-II antagonists, Sarl Ileu8 Ang-II and Sar1 Ala8 Ang-II, but were unaffected by phentolamine, methysergide and diphenhydramine. The response to Ang-I was significantly reduced by treatment with bradykinin-potentiator B, while the response to Ang-II was not influenced. It may be concluded that Ang-I, II and III produce contractions possibly by activation of same Ang-II receptors and that contractions induced by Ang-I are associated, to some extent, with a conversion to Ang-II in the arterial wall.
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  • ANTIARRHYTHMIC EFFECT OF OXPRENOLOL ON HALOTHANE-EPINEPHRINE AND CORONARY LIGATION INDUCED VENTRICULAR ARRHYTHMIAS IN BEAGLE DOGS
    Keitaro HASHIMOTO, Tokumasa TSUKADA, Hiroto MATSUDA, Issei MATSUBARA, ...
    1978 Volume 28 Issue 4 Pages 535-544
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.535
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    Antiarrhythmic effects of oxprenolol, a β-blocker, were studied quantitatively on arrhythmias produced by epinephrine during halothane anesthesia and by two-stage coronary ligation, and were compared to those of other β-blockers, propranolol and Kö 1400, which have been already reported. Though oxprenolol has potent β-blocking activity, the antiarrhythmic effect on halothane-epinephrine arrhythmia was significantly weaker than those of propranolol and Kö 1400. The effective dose of oxprenolol was 60±18 μg/kg (means±S.E., N=6), which is in the range of the so-called β-adrenergic blocking dose. The weaker antiarrhythmic effect of oxprenolol as compared to propranolol and Kö 1400 is probably due to the intrinsic positive chronotropic effect, which is most clearly observed in oxprenolol as compared to the other two drugs. As for two-stage coronary ligation arrhythmia, oxprenolol suppressed only that observed 48 hours after coronary ligation using higher doses (5 to 10 mg/kg). Other β-blockers also showed similar effects. Because of the high doses necessary for the antiarrhythmic effects on the coronary ligation arrhythmia, the mechanism for suppressing the arrhythmia is probably due to the local anesthetic action of the β-blockers.
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  • ON THE HISTAMINE RECEPTOR OF THE CANINE MYOCARDIUM AND CORONARY VASCULATURE
    Keisuke TAKEDA, Yumi KATANO, Yoshito NAKAGAWA, Tokumasa TSUKADA, Toyoz ...
    1978 Volume 28 Issue 4 Pages 545-551
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.545
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    To indentify the histamine-receptors in the canine myocardium, experiments were performed in the canine heart-lung preparation supported by a donor. Smaller doses of histamine produced only an increase in the coronary blood flow. Positive inotropic and chronotropic effects appeared with larger doses. The increase in the coronary blood flow was associated with only a minimal increase in the myocardial oxygen consumption. Pretreatment of the preparation with a prototype H1-receptor antagonist, mepyramine, resulted in an abolishment of the positive chronotropic effect and a partial inhibition of the coronary vasodilatatory effect, indicating that the histamine-receptors in the dog atrium subserving the chronotropic effect are to be classified as H1-type. After a representative H2-receptor antagonist, metiamide, the positive chronotropic effect remained unaffected, while there was a partial inhibition of the coronary vasodilatatory effect. A combined use of both the H1- and H2-receptor antagonists brought about a complete suppression of the positive inotropic and the coronary vasodilatatory effects of histamine. These findings indicate that the histamine-receptors in the coronary vasculature belong to the same type of receptors as those in the peripheral blood vessels, and that those in the canine ventricular myocardium cannot be classified either as H1 or H2.
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  • EFFECT OF DIMERCAPTOSUCCINIC ACID ON TOXICITY OF HABU SNAKE (TRIMERESURUS FLAVOVIRIDIS, HALLOWELL) VENOM
    Norio KURIHARA
    1978 Volume 28 Issue 4 Pages 553-560
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.553
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    Habu venom (HV) incubated with dimercaptosuccinic acid (DMS) or thiosuccinic acid (TMA), was given subcutaneously to mice. The LD50 of HV was 19.7 mg/kg, and after treatment with TMA and DMS, it was 38.1 and 47.1 mg/kg, respectively. The logarithm concentration—mortality curve for the DMS-treated HV shifted to the right compared with the curve for crude HV. The curve for the TMA-treated HV was intermediate between these two. Decimal two mg of HV was then incubated with DMS, and such was given intramuscularly to mice. Hemorrhage and edema which occurred after administration of crude HV were markedly decreased with injection of DMS-treated HV, but the myonecrosis was not greatly affected. At 24 hr after the intramuscular dosing of 1 mg of HV into rats, lymphopenia, acute involution of lymphatic tissue, decrease in liver glycogen and lipid granules in zona fasciculata were apparent, indicating the mark of a stressor. When the DMS-treated venom was administered, the blood picture and histological findings did not differ greatly from the controls. As DMS has marked anti-HV activity, it may be used to investigate treatments for cases of Habu snake bite.
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  • CALCIUM SOURCE FOR CONTRACTILE RESPONSE OF GUINEA PIG TAENIA CAECUM TO CARBACHOL IN A CALCIUM DEFICIENT, POTASSIUM RICH SOLUTION
    Nobuo SHIBATA, Hidenori OHASHI, Tadashi TAKEWAKI, Toshiaki OKADA
    1978 Volume 28 Issue 4 Pages 561-568
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.561
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    The Ca storing site for the carbachol-induced contraction in a high-K medium without adding CaCl2 was further investigated in the guinea pig taenia caecum. La3+ (0.05-0.5 mM) caused an increase in peak tension and relaxation rate in the carbachol contraction but reduced or abolished the response to CaCl2. Simultaneous application of carbachol and CaCl2 produced tension development the trace of which was comparable to the curve obtained by adding graphically the respective traces of the carbachol-induced and Ca-induced tensions. La3+ (0.5 mM) abolished the late, sustained component without appreciable change in the initial, transient contraction. The carbachol contraction persisted after 5 min perfusion of solution containing 0.25 mM EGTA (estimated free Ca2+ concentration less than 10-8 M). The intracellular Ca content was little changed before and after exposure to carbachol. Histamine induced a transient contraction with a dose-dependent amplitude and resulted in a decrease in tension development produced by subsequently applied carbachol. There was an inversely proportional relationship in amplitude between the histamine contraction and the following carbachol contraction, while the sum of tensions raised by both drugs showed little variation. These results favour an intracellular site for the carbachol-sensitive Ca store. Histamine appears to release Ca2+ from the carbachol-sensitive store.
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  • STRAIN DIFFERENCES IN ASPIRIN-INDUCED GASTRIC ULCERATION IN RATS
    Tetsuro URUSHIDANI, Susumu OKABE, Koji TAKEUCHI, Keijiro TAKAGI
    1978 Volume 28 Issue 4 Pages 569-578
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.569
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    We found that there are strain differences in aspirin-induced ulceration in pylorus-ligated rats; the ulcer indices varied, from high to low, in the following order: Donryu>Sprague-Dawley>Wistar. Several experiments including analysis of gastric contents or ionic flux, determination of serum aspirin esterase activity, absorption of aspirin from the stomach, prothrombin time and hexosamine content in gastric mucosa and juice were performed to elucidate the origin of the differences. A significantly higher acid output in Donryu rats, and higher hexosamine content in the gastric mucosa of Wistar rats were noted. However, it appears unlikely that these factors only contribute to the marked strain difference in aspirin-induced ulcers. The possible different sensitivity of gastric mucosal cell itself to aspirin must be considered.
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  • TRYPTAMINERGIC MECHANISM PARTICIPATING IN INDUCTION OF VASOCONSTRICTION BY ADENINE NUCLEOTIDES, ADENOSINE, IMP AND INOSINE IN THE ISOLATED AND BLOOD-PERFUSED HINDLIMB PREPARATION OF THE RAT
    Kazushige SAKAI
    1978 Volume 28 Issue 4 Pages 579-587
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.579
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    The isolated right hindlimb of the recipient rat was perfused at a constant flow rate through the femoral artery with heparinized blood from the carotid artery of a donor. The preparations were under a 99.0±0.8 mmHg of mean perfusion pressure (N=63) and 3.3±0.1 ml/min of blood flow through the right femoral artery. The actions of adenosine, adenosine tri-, die and monophosphate, inosine monophosphate and inosine on the femoral vascular bed were investigated, respectively. These substances injected into the femoral artery, with the exception of inosine, caused a dose-dependent vasoconstriction always preceded by a temporal vasodilatation. Inosine induced only a prompt vasoconstriction. The vasoconstrictor responses to these substances were diminished or reverted to vasodilator ones after repeated administrations and such were significantly prevented by pretreatment with either reserpine or methysergide. These results indicate that all the purines tested induce a vasoconstriction in the femoral vascular bed of the rat through a common (tryptaminergic) mechanism and that such seem to be potent releasers of 5-hydroxytryptamine from peripheral tryptaminergic storage sites.
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  • INFLUENCES OF VERAPAMIL, X-537A, A-23187 AND ADENOSINE 3', 5'-CYCLIC MONOPHOSPHATE ON RELEASE OF 5-HYDROXYTRYPTAMINE FROM RAT BRAIN SLICES
    Hiroko MURAKAMI, Eiko KAJI, Tomio SEGAWA
    1978 Volume 28 Issue 4 Pages 589-596
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.589
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    Influences of verapamil, X-537A, A-23187 and cyclic-AMP on the release of [3H]-5-HT taken up into rat brain slices, were examined. Incubation with 40 mm KCl induced tritium release which was dependent on the presence of Ca2+. Verapamil, which blocks Ca2+ influx in excitable tissues, decreased potassium-induced release of 5-HT. Tritium release induced by ionophore X-537A was not dependent on extracellular Ca2+ while that induced by A-23187 required Ca2+. Cyclic-AMP, dibutyryl cyclic-AMP and theophylline did not significantly stimulate 5-HT release either in the presence or absence of Ca2+.
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  • STUDIES ON CYCLIC NUCLEOTIDES IN THE ADRENAL GLAND VII. CYCLIC AMP SYSTEMS IN THE ADRENAL MEDULLA IN VIVO
    Sumio SHIMA, Yoshiko KAWASHIMA, Masanao HIRAI
    1978 Volume 28 Issue 4 Pages 597-605
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.597
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    3', 5'-cyclic adenosine monophosphate (cyclic AMP) systems in the anesthetized rat adrenal medulla were studied using the technique of a direct infusion of various agents into the adrenal gland, and such is referred to as ‘the retrograde-adrenal vein infusion’ and ‘the intra-adrenal infusion’. A direct administration of acetylcholine into the adrenal gland by the retrograde infusion produced a rapid stimulation of the catecholarnine-release, followed by a delayed activation of the adenylate cyclase in the adrenal medulla. The acetylcholine-induced increase in hormonal secretion and cyclic AMP levels was completely blocked by hexamethonium, indicating the mechanism of nicotinic trans-synaptic stimulation. Intra-adrenal infusion of epinephrine also prevented an increase in cyclic AMP accumulation induced by acetylcholine. This suggests an inhibitory mechanism on the cyclic AMP systems by catecholarnines within the medullary cells. The infusion of propranolol or phentolamine into the gland, in some cases denervated, increased cyclic AMP amounts in the medulla, suggesting a decrease in catecholamine-induced inhibition by a or β-antagonists. These results favor the assumption that the mechanism of catecholamine inhibition of the adenylate cyclase system is mediated by adrenergic interaction. The present studies suggest a mechanism of regulation by catecholamines of the cyclic AMP systems at the early stage of traps-synaptic stimulation, such leading to the delayed increase in the adenylate cyclase activation of the adrenal medulla in vivo.
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  • ROLE OF GASTRIC MOTILITY IN DEVELOPMENT OF STRESS-INDUCED GASTRIC LESIONS OF RATS
    Shingo YANO, Masuo AKAHANE, Masatoshi HARADA
    1978 Volume 28 Issue 4 Pages 607-615
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.607
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    Gastric motility of stressed rats was studied to determine its role in producing stress-induced gastric lesions. Restraint and water immersion resulted in an increase in gastric motility which consisted of an increase in frequency and amplitude of contractions and a rise in gastric tone. This increase reached maximal levels 2 to 4 hr after stress, and persisted thereafter. Formation of gastric lesions was markedly accelerated after occurrence of the increased gastric motility. In contrast, restraint alone neither produced such a vigorous increase in gastric motility, nor were the gastric lesions severe. A continuous infusion of papaverine during restraint and water immersion inhibited increase in frequency and amplitude of gastric contractions and prevented formation of gastric lesions. It is concluded that increased gastric motility is closely associated with marked formation of gastric lesions under conditions of restraint and water immersion stress and is probably a main cause for their vigorous formation, although formation of lesions occurs to a small degree without involvement of gastric motility.
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  • ANTIHYPERTENSIVE EFFECT OF TRICHLORMETHIAZIDE IN SPONTANEOUSLY HYPERTENSIVE RATS
    Motohiko UEDA, Saburo MATSUDA, Kanya TONDA, Kazuki MATSUNAGA
    1978 Volume 28 Issue 4 Pages 617-626
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.617
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    Antihypertensive and diuretic effects of trichlormethiazide (TCM) were investigated in the spontaneously hypertensive rats (SHR). The antihypertensive effect of TCM in an acute experiment was observed in male SHR only at a dose over 10 mg/kg given intraperitoneally and not in female SHR and normotensive Kyoto Wistar rats. to a subacute experiment (6 weeks), TCM retarded the development of hypertension in the male SHR loaded with 1 % saline solution at an oral dose over 1 mg kg-1 day-1 and such had a diuretic effect. Oral administration of TCM and hydrochlorothiazide (HCT) at 10 mg kg-1 day-1 retarded the development of hypertension in the saline loaded female SHR to the same degree, but the relationship between antihypertensive and diuretic effects of both compounds was obscure. Except for decreases of water contents in the thoracic artery and wet weights of hearts, the electrolyte, uric acid, catecholamine and 5-hydroxytryptamine contents in the serum or/and organs were not affected by either TCM or HCT. It is concluded that the antihypertensive effect of TCM and HCT can be observed in SHR with a saline-load, and that the effect may be due to diuretic actions in the male. The relationship was not apparent in female SHR.
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  • CARDIOVASCULAR ACTIONS OF OPTICAL ISOMERS OF PROPRANOLOL
    Junnosuke YAMAMOTO, Atsushi SEKIYA, Hiroshi MAEKAWA, Yoshiko KATO
    1978 Volume 28 Issue 4 Pages 627-631
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.627
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    Effects of the optical isomers of propranolol on blood pressure in the rat, and in the spinal rat during adrenaline infusion were studied to investigate the mechanism of the pressor action of propranolol. Both isomers of propranolol produced a sustained pressor action in the rat and in the spinal rat infused with adrenaline. The magnitude of the pressor action produced by the d- and l-propranolol was proportional to their β-adrenoceptor blocking activities in the heart as was reported by several investigators. It is concluded that the pressor action of propranolol is due to the blockade of the β-adrenoceptors mediating vasodilation in the skeletal muscle vascular beds.
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  • CHANGES IN TISSUE WEIGHT AND CALCIUM CONTENT IN VARIOUS HIGH POTASSIUM SOLUTIONS IN SMOOTH MUSCLE OF GUINEA PIG TAENIA COLI
    Hideaki KARAKI, Tadahiko SUZUKI, Norimoto URAKAWA
    1978 Volume 28 Issue 4 Pages 633-636
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.633
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  • EFFECTS OF SEVERAL ANALGESICS ON THE NUMBER OF VOCALIZATION DISCHARGES OF THE RABBIT
    Shigeo MURAI, Yasumi OGURA
    1978 Volume 28 Issue 4 Pages 636-639
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.636
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  • COMPARISON BETWEEN FLUORIMETRIC AND RADIOCHEMICAL ASSAYS OF IONTOPHORETICALLY RELEASED NORADRENALINE FROM A SEVEN-BARRELED MICROPIPETTE
    Masashi SASA, Seishi IGARASHI, Hiroshi FUJIWARA, Chiyoko INAGAKI
    1978 Volume 28 Issue 4 Pages 639-642
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.639
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  • EFFECTS OF DIFENAMIZOLE ON CONTENT OF CATECHOLAMINES AND METABOLITES IN MOUSE BRAIN
    Toshitaka NABESHIMA, Kazumasa YAMAGUCHI, Tsutomu KAMEYAMA
    1978 Volume 28 Issue 4 Pages 642-646
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.642
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  • GASTRIC SECRETION AND DUODENAL ULCER FORMATION INDUCED BY CYSTEAMINE IN RATS
    Hajime TAMAKI, Yuichi ONODA, Tatsuo KASHIDA
    1978 Volume 28 Issue 4 Pages 647-649
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.647
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  • A POSSIBLE ROLE OF ALPHA ADRENERGIC RECEPTORS IN SALIVATION INDUCED BY ISOPROTERENOL IN MICE
    Hideyo OHSHIKA, Junichiro ENDO, Haruo TAKEMURA, Mamoru TANAKA
    1978 Volume 28 Issue 4 Pages 650-652
    Published: 1978
    Released on J-STAGE: December 19, 2006
    DOIhttps://doi.org/10.1254/jjp.28.650
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