日本薬理学雑誌
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
69 巻 , 6 号
選択された号の論文の12件中1~12を表示しています
  • 久保田 和彦, 勝原 徳寛
    1973 年 69 巻 6 号 p. 835-842
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    Effects of protamine and lanthanum on contractile responses of isolated guinea pig ileum segment or ileum longitudinal muscle strip plus relaxtion responses of the isolated guinea pig taenia coli have been demonstrated herein. Protamine and lanthanum inhibited nonspecifically contractile responses of the ileum to various agonists such as acetylcholine, serotonin, bradykinin, potassium chloride and barium chloride and caused a depression of the maximum response in the acetylcholine dose-response curve. Nonspecific inhibitory actions were similar to papaverine action since the inhibitory actions were overcome easily with addition of calcium ion to the organ bath fluids. Protamine and lanthanum, however, inhibited to a greater degree contractile responses by such agonists as serotonin and bradykinin that act through receptors rather than through membrane. Both protamine and lanthanum blocked the relaxation response by isoproterenol in taenia coli without reducing the resting tone of the muscle. From these findings, it is presumed that protamine and lanthanum have the same mechanism or site of action, that is, they replace the surface site calcium ion on the cell membrane, thus blocking the utilization of calcium which is essential for a receptor-agonist interaction.
  • 西野 仁雄
    1973 年 69 巻 6 号 p. 843-853
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    Using a thermoelectrical method, relationships between the elevation in brain activities caused by CNS stimulants and convulsants and those in regional blood flow were observed. Brain temp. and regional blood flow increased, closely in accordance with the degree of changes in the brain activities, especially just before seizure discharges. There were a few exceptions however, when sympathetic innervation was greatly affected.
  • 西野 仁雄
    1973 年 69 巻 6 号 p. 855-862
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    1) 脳内二,三の部位に電気刺激を加え,それにより惹起される脳波変化に対応する脳局所血流の変動を熱電効果法にて測定した.
    2) RF-ESの全脳覚醒時, HIPP-ESの後発射発現時,またSP-ESの漸加現象出現時の種々の程度の脳波変化時に,その対応した部位において,脳波変化の強弱に応じて局所血流は増加を来した.
    3) 以上の成績は脳局所機能と該局所血流量とは密接かつ微妙に相関している事を示唆している.
  • 和知 正幸, 山浦 和子, 中山 邦夫, 相川 清
    1973 年 69 巻 6 号 p. 863-868
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    Calcium or sodium polystylene sulphonate resin was orally administered to nephrectomized rats, and the survival rate and duration, serum electrolytes and enzyme activities, and other serum chemistry were examined. Both resins clearly increased the survival rate and duration. Ca-resin lowered K+ without effects on Na+, Mg++, and Ca++. Na-resin lowered K+ with increase in Na+ and decrease in Mg++ and Ca++. Neither resin influenced serum enzyme activities, and was practically ineffective regarding serum urea nitrogen, cholesterol, protein and sugar.
  • 小関 良宏, 伊藤 忠信, 中屋 重綱
    1973 年 69 巻 6 号 p. 869-880
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    1) トリチウムでラベルしたesculin (*esculin) をラットおよびモルモットに静注し,臓器内分布を調べた.その結果,血中濃度は経時的な減少を示したが,肝臓,副腎では投与4h後に高値を示した.臓器1g当りの放射活性は副腎が圧倒的に高かった,腎臓や睾丸では放封活性の経時的な減少を示したが,比較的長時間臓器内にとどまった.また臓器1g当りの放射活性は腎臓は副腎に次いで高かった.これにたいして心臓,大脳,小脳および延髄では放射活性は一般に低く,しかも急激な減少を示した.
    2) *esculin静注ラットの肝臓,副腎,睾丸および腎臓のそれぞれの核 (N), ミトコンドリア (Mt), ミクロゾーム (Ms) および上清 (S) の各画分における*esculinの経時的分布を調べた.
    肝臓では投与30m後にはMs, S-画分に, 1h後にはMt-画分に高いとり込みがみられた.副腎では1h後はS-画分が最も高く,次がN-画分であった, 4h後ではMt-画分が高く次がMs-画分であった.睾丸では1h後MtとN-画分が高かったが, Mt-画分はその後急激に減少した. N-画分ではその後でもなお比較的高い放射活性を示した.腎臓の皮質では30m後のS-画分のみが最も高い値を示し,その他の画分はいずれも低値であった.髄質では4h後のMt-画分が最も高く,次がN-画分であった.その他の画分は皮質の場合と同様であった.
    3) *esculinをラットおよびモルモットの静脈内または胃内に投与したのち,尿および糞に排泄される代謝物をペーパークロマトグラフィーで分離した.
    ラット尿への排泄は静脈の場合,1hおよび4h後ともesculinが一番多く,次がesculin (Rf=0.49±0.03) よりRf値の低い物質であった. 20h後ではesculetin (Rf=0.75±0.03) よりRf値の高い物質 (Rf=0.84) が多かった.また胃内投与の場合, 4h後ではesculinが一番多かった.しかし静注の場合と異なりesculetinが次に多く排泄された.モルモットの尿の場合もラット尿と同様な傾向を示したが,静注4hおよび20h後ではesculinのほかにesculinよりRfの高い物質の排泄が多かった.
    ラット糞への排泄は静脈,胃内投与ともesculin, esculetinおよびこれよりRf値の高い物質が排泄された.これにたいしてモルモットの静脈内投与の場合は4h後ではラット糞と同様な傾向を示したが, 20h後ではRf値の極めて低い物質 (Rf=0.18) が最も多く,次がesculinよりRf値の高い物質 (Rf=0.67) とesculetinとであった.
  • 前田 隆史
    1973 年 69 巻 6 号 p. 881-897
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    I. Action of spasmogens. Evidence has been obtained suggesting that (1) for all of the spasmogens (K, ACh, Ba) tested, phasic contraction is produced by Ca release while tonic contraction is maintained by the energy-dependent influx of Ca. (2) Only in case of Ba, is a direct stimulation to the contractile protein of muscle partly concerned with contraction. This is implied by a residual contraction by Ba in the Ca-free bath solution. (3) Ba releases Ca from the store of easily releasable Ca, as K and ACh, and in addition from the store of less easily releasable Ca. II. Action of antispasmodics. As the result of various experiments, it was concluded that (1) antispasmodic action of isoproterenol is attributed to the depression of muscle cell membrane, that is, due to the pseudo-competitive (or functional) inhibition of release and then influx of Ca with increased concentrations used. (2) Antispasmodic actions of papaverine and chlorpromazine are attributed to the depression of membrane (competitive inhibition of influx and then release of Ca) followed by a non-competitive inhibition against the contracting action of Ca on the muscle contractile system with increase of concentrations.
  • 藤村 一, 鶴見 介登, 安部 彰, 林 元英, 中野 万正
    1973 年 69 巻 6 号 p. 899-918
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    In a previous paper, it was reported that F-1, a new non-steroidal compound, had a potent inhibitory effect similar to that of fiufenamic acid (FA) and phenylbutazone (PB) on experimental acute inflammation. General pharmacological actions of F-1 are described herein. Analgesic action of F-1 was similar to that of mefenamic acid (MA) and more potent than that of FA and PB. F-1 did not show significant activities in such tests as locomotion, rotarod, anticonvulsion, hypnotic potentiation to barbiturates, hypothermic and anti-pyretic action. It appeared, therefore, not to have side effects on the central nervous system. It was also free of any effect on the cardiovascular and respiratory systems, renal function, blood coagulation and blood sugar level in doses causing anti-inflammatory effect. F-1 inhibited isolated intestinal movement and relaxed smooth muscle in a high concentration and did not show specific antagonistic action on such spasmogens as histamine, acetylcholine and BaCl2. F-1 inhibited contraction of the intestine by 5-HT and diarrhea by 5-HTP. Therefore, F-1 was found to have weak anti-serotonic action. F-1 was found to have potent anti-inflammatory action and few side effects. It may be considered that F-1 can be classified as a non-steroidal analgesic and anti-inflammatory agent.
  • 藤村 一, 鶴見 介登, 野崎 正勝, 林 元英, 中野 万正, 岩田 忠彦
    1973 年 69 巻 6 号 p. 919-929
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    Since the report of Mizushima in which it was stated that a number of acidic anti-inflammatory drugs inhibited heat denaturation of protein, the interaction between anti-inflammatory agents and protein has been studied in various materials. F-1, a non-steroidal acidic analgesic and anti-inflammatory agent, was also investigated concerning the interaction with protein. F-i inhibited heat denaturation of bovin serum albumin (BSA) at pH 5.3 and the activity was more potent than that of phenylbutazone and similar to fenamates. F-i had a more potent inhibitory effect than phenylbutazone and fenamates on binding of pyridoxal-5-phosphoric acid and trinitrobenzaldehyde to BSA. Interaction of F-1 with the above BSA correlated with the inhibitory effect on hypotonic-hyperthermic hemolysis and enzyme activity of trypsin and α-chymotrypsin. F-1 showed a similar affinity to fenamates on erythrocytes in rats. Serum protein in adjuvant arthritis rats differed from control serum (decrease of albumin contents and A/G ratio, increase of haptoprotein and heat denaturation). F-1 improved qualitatively and quantitatively those serum changes. From the above results, F-1 was found to bind with protein and to have the same properties as known acidic antiinflammatory agents. Mode of interaction of F-1 differed to some extent from fenamates.
  • 田代 義礼, 佐藤 勝, 長南 義勝, 若林 一雄, 岩城 利一郎, 福田 芳郎, 北川 晴雄
    1973 年 69 巻 6 号 p. 931-945
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    In order to examine the effect of sodium hydrodextran sulfate (HDS) on experimental atherosclerosis spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR) were fed a high-fat diet with and without the drug. Blood samples were collected for 5 months to measure serum levels of cholesterol, triglyceride and clearing factor lipase activity. Effect of HDS on certain blood factors were as follows: 1) HDS inhibited the increase of serum cholesterol levels in rats. 2) HDS did not change the triglyceride concentration. 3) HDS elevated the clearing factor lipase activity. 4) A high-fat diet increased the intimal thickening of arteries in SHR. 5) Intimal thickening of arteries decreased slightly in the HDS treated group.
  • 鈴木 良雄, 伊藤 磯人, 伊藤 幹雄, 山上 一香
    1973 年 69 巻 6 号 p. 947-968
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    In adjuvant arthritic rats, the relationship between hind paw swelling and mucopolysac-charase (β-glucuronidase, N-acetyl-β-glucosaminidase and lysozyme), protease (pH 3.1 and7.0) and collagenolytic activities in serum and hind paws was investigated. Furthermore, the effects of various anti-inflammatory drugs (phenylbutazone, bucolome, indomethacin, prednisolone, azathioprine, chloroquine diphosphate and a anti-plasmin agent, DV-1006) administered orally once a day were examined 3 and 21 days after adjuvant injection. The swelling of right (injected) hind paw increased remarkably after adjuvant injection and reached a first peak on day 3, after which it decreased gradually. About 10 days later, however, it began to increase again and the swelling of left (non-injected) hind paw also occurred simultaneously. The swelling reached maximum intensity by day 21 in the right hind paw and by day 28 in the left. The activities of three mucopolysaccharases and protease at pH 3.1 in both hind paws changed as did swelling of each hind paw after adjuvant injection. Changes of these enzyme activities in serum ran parallel with those of right paw swelling. On the other hand, the collagenolytic activity in both hind paws increased rapidly and remarkably after 14 days. On day 3, swelling of the right paw was strongly inhibited by the drugs except for azathioprine, chloroquine diphosphate and DV-1006. On day 21, the swelling of both hind paws was remarkably inhibited by all drugs except chloroquine diphosphate. On day 21, a parallel relationship was proved between anti-swelling activity and anti-mucopolysaccharase or anti-protease (pH 3.1) activity in left hind paw and serum by drugs, although not necessarily on day 3. On day 21, collagenolytic activity was inhibited by all drugs. These results suggest that these lysosomal enzymes are main mediators in the development of a secondary lesion in adjuvant arthritic rats.
  • 江頭 亨, 金子 修, 沢田 寿一, 金 慶培, 定岡 啓三, 庄 貞行
    1973 年 69 巻 6 号 p. 969-976
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    The effects on Monoamine Oxidase (MAO) in rat brain and liver and production of methemoglobin (Met-Hb) in blood by the administration of NaNO2 and NH2OH have been studied and the following results were obtained : Administration of NaNO2 and NH2OH caused a marked increase in the blood level of Met-Hb. Met-Hb in blood was 6.4 and 4.5 g/dl after i. p. administration of 100mg/kg NaNO2 and NH2OH, respectively. The blood level of Met-Hb reached a maximum at 15 and 30min following i. p. administration of 50mg/kg NaNO2 and NH2OH, respectively and then disappered gradually. Rats were administered NaNO2 i. p. in a dose of 50mg/kg/day for 30 days. The blood level of Met-Hb was increased slightly on the 3rd-4th day. The increasing MAO activity in rat liver was observed immediately and on the 2nd day following i. p. administration of 50mg/kg NaNO2 when tyramine was used as substrate. When benzylamine was used as substrate, MAO activity increased at 2-3 hours and on the 4th day. MAO activity in rat brain markedly increased on the 3 rd-4th day following i. p. administration of NaNO2 with tyramine as substrate. Similar results were obtained when serotonin (5-HT) was used as substrate. Rats were administered NH2OH i. p. in a dose of 50mg/kg/day for 30 days. The blood level of Met-Hb was increased slightly on the 3rd-4 th day. When tyramine was used as substrate, increasing MAO activity was observed on the 5th day of administration. Significant change of MAO activity was not observed when benzylamine was used as substrate. In case of brain, MAO activity increased on the 4th-6th day and decreased 1st-2nd day and 14th-20th day of administration when tyramine was used as substrate. Almost similar results were obtained when 5-HT was used as substrate.
  • 高崎 浩一朗, 金子 美恵子, 藤井 富男, 小林 英夫
    1973 年 69 巻 6 号 p. 977-994
    発行日: 1973/11/20
    公開日: 2010/07/30
    ジャーナル フリー
    新合成異環状カルボン酸 (NDM) 誘導体の主として経口投与による血糖低下作用について検討し次のごとき結果をえた.
    1) ブドウ糖負荷ラットにおいて, 3または5位にmethyl基,あるいはこれとともに5または3位にcarboxyl基, carboxylic acidおよびcarboxylic acid amideなどが導入された誘導体は強い血糖低下作用を有していた.
    2) ウサギにおける耐糖力試験では, isoxazole系誘導体は軽度陰性, pyrazole系誘導体は軽度陽性傾向を示した.
    3) マウスにおける低血糖試験では,ブドウ糖の投与によってNDM誘導体によるLD50や死亡までの時間は有意な変化をうけなかった.
    4)ウサギにおけるハソピング試験では, isoxazole系, pyrazole系誘導体ともに陽性傾向を示した.
    5) イヌとウサギの正常血糖値および膵臓摘出ラットの高血糖値は, NDM誘導体投与によってはほとんど影響をうけなかった.
    6) ウサギの正常血糖値およびalloxan糖尿病ウサギの高血糖値は, NDM誘導体の投与によってはほとんど有意義な低下現象は認められなかった.
    7) エピネフリン過血糖試験では, isoxazole系誘導体では陽性傾向, pyrazole系誘導体は陰性傾向を示した.
    8) ラットにおいて, NDM誘導体は,肝臓glycogen量を低下させえなかったが,ブドウ糖投与による肝臓glycogen量の増加作用を抑制した.
    9) ブドウ糖負荷副腎摘出ラットでは,同じブドウ糖負荷正常ラットにおけるとほぼ同じ比率で血糖低下作用をおこした.
    10)ブドウ糖負荷ラットにおいて, tolbutamide, oxalacetic acidまたはinsulinとNDM誘導体の併用による血糖低下作用の協力増強効果は認められなかった.
    11) ウサギの正常遊離脂肪酸量はNDM誘導体投与によって軽度の増加をおこしたり,またはわずかな減少をおこした.
    12) ウサギにおいてブドウ糖投与時, NDM誘導体によって糖の尿中排泄量が著明に増加された.
    以上の結果から,異項環状カルボン酸誘導体は,特に外因性ブドウ糖の著明な尿中排泄促進作用によって血糖値を低下させる作用を有すると考えられるが,内因性血糖上昇作用に対しては抑制効果は少ないものと考えれる.
feedback
Top