The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
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Volume 34, Issue 1
Displaying 1-20 of 20 articles from this issue
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  • Comparison of the Antinociceptive Effect between the Cyclic Dipeptide Cyclo [Tyr(Et)-Homoarginine] and the Linear Dipeptide Boc-Tyr(Et)-Homoarginine-OMe in Rats
    Takumi SATO, Shinobu SAKURADA, Tsukasa SAKURADA, Kensuke KISARA, Yusuk ...
    1984 Volume 34 Issue 1 Pages 1-8
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.1
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    The antinociceptive effect of the cyclic dipeptide cyclo[Tyr(Et)-homoarginine] (C.TEHA) was examined utilizing the tail flick test and the digitus pinching test in rats in comparison with the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe (B.TEHM). Though both dipeptides administered into the lateral, 3rd and 4th cerebroventricles produced antinociceptive effects equipotent to morphine, except for the 4th cerebroventricular administration of B.TEHM, the administration into the spinal subarachnoid space was without effect. The effect of B.TEHM was completely antagonized by the pretreatment of naloxone (i.p.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the most potent. However, naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipeptides act on the upper brain stem, especially around the 3rd cerebroventricle. Moreover, it was also thought that the effect of B.TEHM may be involved in the brain opioid system, and that of C.TEHA can be produced via a naloxone-resistant opioid system or a nonopioid system.
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  • Effect of N-5' on Histamine Release from Rat Peritoneal Exudate Cells Induced by Calcium lonophore and ATP
    Arao UJIIE, Masami KOJIMA, Jun NAITO, Masayuki NAKAZAWA, Akihide KODA
    1984 Volume 34 Issue 1 Pages 9-14
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.9
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    We studied the effect of N-(3, 4-dimethoxycinnamoyl)anthranilic acid (N-5'), an orally applicable anti-allergic drug, on the histamine release induced by calcium ionophores (A23187 and X537A) and ATP from rat peritoneal exudate cells (PEC). X537A (0.1-33.3 μg/ml) induced histamine release in a concentrationrelated manner, and 2.0 μg/ml of X537A induced release to the same extent as allergic histamine release. Histamine release induced by 2.0 μg/ml of X537A increased with longer incubation time, reaching a peak of about 100% at 120 min. N-5' had no effect on histamine release induced by X537A at the concentrations used (1-1000 μM), but DSCG exhibited significant inhibition at 1-100 μM. A23187 (0.05-0.5 μg/ml) induced histamine release in a concentration-related manner, and it seemed that 0.033 μg/ml of A23187 induces the same degree of histamine release as the allergic one. A23187 induced rapid histamine release which attained maximum 1 min after the addition. N-5' exhibited a significant concentration-dependent inhibitory effect on histamine release induced by A23187, and DSCG also exhibited significant inhibition (10 and 1000 μM). N-5' significantly inhibited histamine release induced by 100 μM ATP. These results indicate that N-5' and DSCG effect the histamine release induced by lonophore A23187 and X537A by different manners, and they suggest the possibility that N-5' inhibits some Ca++-dependent processes in histamine release, including the influx of Ca++ into cells, which is a trigger of the A23187 and ATP effects.
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  • Effects of Histaminergic Drugs on Muricide Induced by Thiamine Deficiency
    Kenji ONODERA, Yasumi OGURA
    1984 Volume 34 Issue 1 Pages 15-21
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.15
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    Male Wistar rats maintained on a thiamine deficient diet showed mouse-killing aggression (muricide). On the 30th day of experimental feeding, the incidence of this muricide was about 70%. Intracerebroventricular histamine suppressed the muricide induced by thiamine deficiency in a dose-dependent manner. Histamine H1-receptor blocking agents such as diphenhydramine, promethazine and chlorpheniramine also showed muricidal suppression, but astemizole which lacks central effects did not show muricidal suppression. Mianserin and iprindole showed muricidal suppression, but metiamide i.p. did not. On the 20th day of experimental feeding, the incidence of this muricide was 45.5%. Histamine synthesis inhibitors such as brocresine or α-fluoromethylhistidine could not enhance the muricide on non-killer-rats, but really suppressed the thiamine deficient killer-rats. The results of this paper suggested that muricide induced by thiamine deficiency is not mediated by the central histaminergic system, but pharmacologically characterized by antidepressants, antihistamines and histamine synthesis inhibitors.
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  • Effect of (±)-2-[p-(2-Thenoyl) Phenyl] Propionic Acid (Suprofen) on Experimental Allergic Reactions
    Fusayuki YOKOYA, Tamaki NAKAYAMA, Kenji SAKAMOTO, Kazuo OHHIRA, Yasuhi ...
    1984 Volume 34 Issue 1 Pages 23-31
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.23
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    The effects of (±)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen), a new anti-inflammatory agent, on experimental allergic reaction and antibody formation were examined. The action was compared with those of ketoprofen, ibuprofen, indomethacin, tranilast, chlorpheniramine, prednisolone and/or cyclophosphamide. Suprofen inhibited homologous PCA in rats, immunological histamine release from rat peritoneal mast cells and guinea pig lung tissues, Forssman cutaneous vasculitis (FCV) and the Arthus reaction in guinea pigs. The potency for inhibition of the PCA reaction was similar to that of ketoprofen and more potent than ibuprofen and trailast. As for the release of anaphylactic mediators, suprofen was less potent than tranilast in terms of histamine release, but not the release of the slow reacting substance of anaphylaxis (SRS-A). Suprofen inhibited FCA more potently than other nonsteroidal anti-inflammatory drugs (NSAID). The inhibition of the Arthus reaction by suprofen was similar to those of other NSAID and prednisolone. Suprofen hardly affected delayed hypersensitivity in guinea pigs and antibody (lgM or lgE) formation in mice or rats.
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  • Studies on Antinephritic Effect of Mizoribine (p-INN, Bredinin®), a New Immunosuppressive Agent, and Azathioprine (2) Effect on Crescentic-Type Anti-GBM Nephritis in Rats
    Kyoko OKAMOTO, Mikio ITO, Yoshio SUZUKI
    1984 Volume 34 Issue 1 Pages 33-41
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.33
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    Crescentic-type nephritis was induced in rats by immunizing with rabbit γ-globulin following i.v.injection of rabbit anti-rat glomerular basement membrane (anti-GBM) serum. The antinephritic effect of mizoribine was compared to that of azathioprine by administration from the 2nd day after the injection of anti-GBM serum to the 23rd day (Experiment I) and from the 15th to the 38th day (Experiment II). The experiment I assessment on the 24th day revealed that mizoribine at a dose of 7.5 mg/kg/day p.o. remarkably reduced plasma cholesterol level, wet kidney weight and glomerular histopathological changes (i.e., crescent formation and fibrinoid deposition). In addition, mizoribine at this dose also tended to reduce urinary protein excretion and the adhesion of capillary walls to Bowman's capsule. At a dose of 5 mg/kg/day p.o., mizoribine significantly reduced kidney weight and crescent formation. On the other hand, azathioprine at a dose of 20 mg/kg/day p.o. had a tendency to reduce these biochemical and histopathological parameters. In the experiment II assessment on the 39th day, the effects of both drugs were somewhat diminished compared to those in experiment I. Mizoribine strikingly inhibited the crescent formation with 5 and 7.5 mg/kg/day p.o. and inhibited the fibrinoid deposition with a dose of 7.5 mg/kg/day p.o. Azathioprine at a dose of 20 mg/kg/day p.o. was prone to reduce histopathological parameters. The above data indicate that mizoribine may be a useful new immunosuppressive agent for rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with the extensive formation of crescents.
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  • A Technique for the Perfusion of the Isolated Rabbit Pancreas
    Toshiyuki SAITO
    1984 Volume 34 Issue 1 Pages 43-50
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.43
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    The present paper describes a technique for the vascular perfusion of the isolated rabbit pancreas, evidence for the viability of the perfused gland and the responses to stimulation by secretin (Sc) and acetylcholine (ACh). The isolated rabbit pancreas was perfused at a constant pressure through the superior mesenteric artery with Krebs-Henseleit solution. The perfused gland, kept in a viable state over the perfusion period of 7 hr, secreted pancreatic juice spontaneously; the juice flow increased and the amylase output decreased gradually for approx. 2 hr after the beginning of perfusion, following the flow and output relatively constantly for several hours. The single infusion of Sc caused a prolonged flow of the pancreatic juice with an increase in the bicarbonate concentration and a decrease in the chloride concentration, though Sc was present in the perfusate for only a short time. The single infusion of ACh was not effective on the juice flow, but immediately increased the amylase output dose-dependently. These results indicate that the saline-perfused preparation of the rabbit pancreas has wide applications in experimental studies on the exocrine pancreas.
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  • The Effects of Ca Antagonists, Manganese and Lanthanum on Cooling-Induced Contracture of Depolarized Vas Deferens
    Satoru SUNANO
    1984 Volume 34 Issue 1 Pages 51-56
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.51
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    Lowering of temperature applied during the course of the tonic contraction of high-K-induced contracture of guinea-pig vas deferens induced an increase in tension which was sensitive to extracellular Ca. Verapamil and nifedipine inhibited the tonic contraction and cooling-induced tension development. Mn2+ and La3+ also showed inhibiting actions on the tonic contraction, which, however, was followed by slow re-elevation of the tension. Cooling treatment caused relaxation in the presence of either ion, which increased with repetition of the cooling treatment. By rewarming the preparation, a phasic contraction, which increased in height with repetition of the treatment, was observed. These effects in the presence of Mn2+ or La3+ were also observed in the absence of Ca or in preparations treated with caffeine in Ca-free solution (Ca-deprived preparation). Verapamil was capable of depressing these effects of Mn2+ and La3+. These results suggest the involvement of influxed Ca in the initiation of tension development by cooling. The decrease of extrusion through the cell membrane and/or uptake by intracellular binding sites at low temperature may be the cause of the cooling-induced tension development. Mn2+ or La3+ induces the tension development by their direct actions on contractile proteins which are differently affected by the changes in temperature.
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  • Effects of Palytoxin on Na, K and ATP Contents of Vascular Smooth Muscle of Rabbit Aorta
    Hiroshi OZAKI, Hiromi NAGASE, Katsuaki ITO, Norimoto URAKAWA
    1984 Volume 34 Issue 1 Pages 57-66
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.57
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    Palytoxin (PTX) at concentrations higher than 10-9 M increased tissue Na and decreased tissue K contents in the smooth muscle of rabbit aorta. The decrease in the tissue K content induced by PTX (10-8 M) was complete within 1 hr. Saponin (1 mg/ml) and Triton X-100 (0.1% wt./vol.) also rapidly decreased the tissue K content. On the other hand, a high concentration of ouabain (10-3 M) did not change the tissue K content within 1 hr of application, and the maximum loss of K was obtained after 6 hr. Loss of tissue Na into Na- and K-free solution from Na loaded muscle was accelerated by PTX (10-8 M). The PTX-induced increase in loss of Na was inhibited in proportion to the decrease in the temperature from 37 to 10°C, while the loss of Na in the absence of PTX was almost completely inhibited at 24°C. Decrease in the wet weight of the muscle induced by hyperosmotic solution was inhibited by pretreatment with PTX (10-8 M) or saponin (1 mg/ml) for 1 hr. PTX (10-9 and 10-8 M) had no effect on the ATP content of the muscle. However, PTX at concentrations above 10-7 M reduced the ATP content, and a significant amount of ATP was detected in the incubation medium. Saponin (1 mg/ml) and Triton X-100 (0.2% wt./vol.) induced a release of Na from liposomes prepared with synthesized lecithin or total lipids of rabbit red blood cells. However, no Na leak was induced by PTX (10-8-10-6 M) in these liposomes. These results suggest that PTX at low concentrations (10-9-10-8 M) increases the membrane permeability of vascular smooth muscle cells to Na and K ions. At higher concentrations (10-7-10-6 M), PTX seems to form pores which are permeable to a larger molecule like ATP. The results further suggest that the mode of action of PTX is different from that of saponin or detergent.
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  • Inhibition of Electrically-Induced Vocalization in Adjuvant Arthritic Rats as a Novel Method for Evaluating Analgesic Drugs
    Shigeru OKUYAMA, Hironaka AIHARA
    1984 Volume 34 Issue 1 Pages 67-77
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.67
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    A new method for the evaluation of analgesic drugs in normal rats and in rats with hyperalgesia induced by adjuvant was developed using the vocalization response as an indicator of pain due to electrical shock. It was demonstrated that at ED50 doses, nonsteroidal anti-inflammatory drugs (NSAIDs), narcotic analgesic drugs and narcotic agonist/antagonist type analgesic drugs were effective, but pure narcotic antagonist drugs, CNS-acting drugs and anti-inflammatory steroid were ineffective. Acidic NSAIDs, except aspirin, were more effective in adjuvant arthritic rats than normals but other analgesic drugs had roughly the same effect in both. It was suggested that the acidic NSAIDs specifically inhibit inflammatory pain. Moreover, the vocalization response under adjuvant treatment is useful for the quantitative measurement of analgesics.
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  • Hepatic 7-Alkoxycoumarin O-Dealkylase in Mice: Induction by β-Naphthoflavone of Hepatic Enzyme Activity
    Takashi MATSUBARA, Akira TOUCHI, Masao MASUI, Emiko YOSHIHARA, Akira A ...
    1984 Volume 34 Issue 1 Pages 79-88
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.79
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    Hepatic 7-alkoxycoumarin O-dealkylation activities in control and β-naphthoflavone-pretreated mice were determined. The O-demethylation and O-deethylation activities of 7-alkoxycoumarin in control mice were almost the same values, while the O-depropylation activity was lower than those of the other reactions. The O-dealkylase activity varied markedly among the 18 strains of mice surveyed, and strain-dependent differences in the cytochrome P-450 content were also detected among the strains. β-Naphthoflavone induced O-dealkylation activity, especially O-deethylation and O-depropylation activities, only in ddY, DS and its substrains (A2-3, A3-1, C1-2 and Nh/+), C3H/He and C57BL/6J strains, but not in DBA/2, BALB/c and KYF/2 strains. The former strains of mice are thus classified as “responsive strains” to β-naphthoflavone and the latter as “non-responsive strains”. The O-dealkylase activity in other strains of mice were not clear in responsiveness to β-naphthoflavone. The hepatic cytochrome P-450 content in responsive strains also increased upon pretreatment of the animals with β-haphthoflavone. The results indicate marked strain differences in basal and β-naphthoflavone-induced activity of hepatic 7-alkoxycoumarin O-dealkylase in mice.
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  • Effect of an Anti-Ulcer Agent, 2'-Carboxymethoxy-4, 4'-Bis (3-Methyl-2-Butenyloxy) Chalcone (SU-88), on the Biosynthesis of Gastric Sulfated Mucosubstances in Restrained and Water-Immersed Rats
    Toshio SUWA, Kiyomi FUKUSHIMA, Kazuaki KYOGOKU, Hiroharu EDO, Yo MORI
    1984 Volume 34 Issue 1 Pages 89-94
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.89
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    2'-Carboxymethoxy-4, 4'-bis(3-methyl-2-butenyloxy) chalcone (SU-88) has an anti-ulcer effect which is considered to increase the resistant factors of the gastric mucosa. In order to clarify the mechanism of the action of SU-88, the biosynthesis of gastric sulfated mucosubstances (SMS) in vivo and in vitro was investigated in rats with gastric erosion induced by restraint and water-immersion. The incorporation of 35S-sulfate into gastric SMS was significantly reduced 18 hr after the onset of stress. Pretreatment with SU-88 (500 mg/kg, p.o., x10 days) prevented a reduction in the incorporation of 35S-sulfate due to stress when 35S-sulfate was administered in vivo. On the contrary, the incorporating activity of 35S-sulfate into the SMS in the isolated rat gastric mucosa with erosion was significantly increased 12 hr after the onset of stress, as compared with that of the control group in vitro. The incorporation of 35S-sulfate into the SMS was still further increased by the oral administration of SU-88. The mode of action of SU-88 on the biosynthesis of SMS was discussed.
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  • Potentiating Effect of Methysergide on Norepinephrine-Induced Constriction of the Isolated Internal Carotid Artery of the Dog
    Tsutomu TSUJI, Shigetoshi CHIBA
    1984 Volume 34 Issue 1 Pages 95-100
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.95
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    The stainless steel cannula inserting method was used to examine the effects of methysergide on 5-hydroxytryptamine (5-HT)-and norepinephrine-induced vasoconstriction in the isolated internal carotid artery of the dog. 5-HT, at a dose of 0.3 μg, induced a marked increase in perfusion pressure, usually over 100 mm Hg. On the other hand, norepinephrine produced a relatively small increase in perfusion pressure (20-40 mm Hg) at a large dose of 10 μg. Methysergide inhibited 5-HT-induced vasconstriction. Norepinephrine-induced vasoconstriction was significantly potentiated by treatment with methysergide and blocked by phentolamine. Methysergide also enhanced the vasoconstrictor response to potassium chloride. Thus, it is suggested that the potentiating effect of methysergide on norepinephrine-induced vasoconstriction may partially be due to activation of the inward calcium channel of the internal carotid artery.
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  • Effects of Morphine, Clonidine and Papaverine on Synaptosomal 45Ca Uptake and Antinociceptive Action in Rats
    Fukio KONNO, Issei TAKAYANAGI
    1984 Volume 34 Issue 1 Pages 101-107
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.101
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    We studied the relationship between the inhibition of extracellular 45Ca2+ uptake into synaptosomes and the antinociceptive action induced by morphine, clonidine and papaverine in rats. The antinociceptive action induced by clonidine was as potent as that by morphine, but that by papaverine was less potent than those by morphine and clonidine. Antinociceptive action by morphine was considerably potentiated by the simultaneous administration of clonidine. However, the antinociceptive actions induced by morphine and clonidine were found to be mediated through different receptor mechanisms. Although the pretreatment by papaverine blocked the morphine-induced antinociception, the inhibition induced by papaverine was not found to be mediated through the opiate receptor because papaverine did not displace [3H]-dihydromorphine binding to the membrane fraction from rat brain. Papaverine also inhibited the antinociceptive action induced by clonidine. Morphine inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake by a naloxone-reversible process. Papaverine also strongly inhibited the veratrine-stimulated synaptosomal 45Ca2+ uptake, while clonidine had virtually no effect. The inhibition of synaptosomal 45Ca2+ uptake induced by morphine was not increased by simultaneous addition of clonidine. The strong inhibitions of synaptosomal 45Ca2+ uptake were still observed by simultaneous addition of papaverine with morphine and clonidine. These results suggest that it is difficult to account for the drugs-induced antinociception by the inhibition of extracellular Ca2+ uptake into the synaptosomes only because papaverine inhibits the manifestation of the antiociceptive actions induced by morphine and clonidine mediated through mechanisms other than the inhibition of extracellular 45Ca2+ uptake into the synaptosomes.
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  • The Effects of Phospholipase and 2-Chloroadenosine Treatments on α2-Adrenoceptors in Rat Vas Deferens
    Yasuhiro WATANABE, Yoshiro KAMINOH, Toshifumi KAGIYA, Hidehiko KAWABAT ...
    1984 Volume 34 Issue 1 Pages 109-112
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.109
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  • Changes in Glycosylated Hemoglobin in Short-and Semi Long-Term Streptozotocin-Diabetic Mice and Rats
    Emiko FUJII, Teruko NOMOTO
    1984 Volume 34 Issue 1 Pages 113-115
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.113
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  • Influences of Taurine on Functions of Rat Neutrophils
    Midori MASUDA, Kazuyoshi HORISAKA, Takemi KOEDA
    1984 Volume 34 Issue 1 Pages 116-118
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.116
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  • Effects of Cycloheximide and Repeated TRH Administration on TRH Receptors in the Mouse Brain
    Norio OGAWA, Sachiko MIZUNO, Setsuko OHARA, Hiroo KURODA
    1984 Volume 34 Issue 1 Pages 119-121
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.119
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  • Chloroform Counteracts Effect of Cholesterol on Microviscosity of Lipid Vesicle
    Chieko OKUDA, Masao MIYAZAKI, Kinya KURIYAMA
    1984 Volume 34 Issue 1 Pages 122-124
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.122
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  • Time Course of Brain MHPG-S04 Level Following Stimulation of Pre-and Post-Synapitic α-Adrenoceptors by Clonidine
    Yasuko KOHNO, Masatoshi TANAKA, Gary B. GLAVIN, Yoshio HOAKI, Akira TS ...
    1984 Volume 34 Issue 1 Pages 125-127
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.125
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  • Effect of Lithium on Organic Ion Transport in Rat Kidney Cortical Slices
    Munekazu GEMBA, Naoko MIKURIYA, Akemi TACHIBANA, Mayumi NAKAJIMA
    1984 Volume 34 Issue 1 Pages 128-130
    Published: 1984
    Released on J-STAGE: November 07, 2006
    DOIhttps://doi.org/10.1254/jjp.34.128
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