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Vinod BHARGAVA
1973 Volume 23 Issue 4 Pages
431-436
Published: 1973
Released on J-STAGE: December 19, 2006
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In rats anaesthetized with pentobarbitone, somatosensory evoked potentials produced by stimulation of the contralateral or the ipsilateral forepaw were used as a measure of activity in different neuronal population. Drugs were applied to the pial surface by using cortical-cup technique and changes were measured in the somatosensory evoked responses. Cortical application of acetylcholine and acetyl-β-methylcholine increased the amplitude of the repetitive after discharges. No significant effect was seen on the primary complex. The effect of cholinomimetic drugs was blocked by benactyzine. It is suggested that the afferent pathways responsible for the repetitive after discharges involve a cholinergic mechanism.
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O.P. SETHI, O.D. GULATI
1973 Volume 23 Issue 4 Pages
437-451
Published: 1973
Released on J-STAGE: December 19, 2006
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Hexamethonium and tetraethylammonium (TEA) produced parallel shifts (equilibrium blockade) of nicotine and dimethylphenylpiperazinium dose-response curves at all dose levels on isolated rabbit and guinea pig ileum preparations, while mecamylamine, pempidine, chlorisondamine and pentolinium produced parallel shifts at lower doses and nonparallel shifts (nonequilibrium blockade) at higher dose levels. Hexamethonium and TEA protected against the nonequilibrium blockade by mecamylamine, pempidine, chlorisondamine and pentolinium. Dose ratios for the combination of hexamethonium with TEA, with chlorisondamine or with pentolinium were consistent with competitive type of blockade. Dose ratios for the combination of hexamethonium with mecamylamine or with pempidine were not consistent with the noncompetitive type of blockade. It is concluded, that hexamethonium and TEA act as equilibrium competitive ganglion blockers while mecamylamine, pempidine, chlorisondamine and pentolinium act as nonequilibrium competitive ganglion blockers.
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Shogo TOMISAWA, Norimitsu L. SATO
1973 Volume 23 Issue 4 Pages
453-458
Published: 1973
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Protein content of the peritoneal fluid of mice with induced inflammation was determined using a biuret reagent. The amount of protein in the peritoneal fluid was maximal at two hr after the i.p. injection of 1.2% acetic acid solution when the content of protein was tenfold that of normal mice. The increase in protein content in the peritoneal fluid corresponded well with the dye content leaked from the vascular bed. The anti-inflammatory drugs tested were curative as well as preventive on the increased vascular permeability.
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Katsunori OGURO, Katsumi KUBOTA, Tomohiko KIMURA, Koroku HASHIMOTO
1973 Volume 23 Issue 4 Pages
459-466
Published: 1973
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Effects of various coronary vasodilators were compared with those of isoprenaline in modified Langendorff's dog heart preparation with cross-circulation by a donor dog. Coronary vasodilators used in this study all induced a significant increase in the rate of coronary blood flow with a decrease in the A-V O
2 difference. The coronary vasodilating activity was in the following order; nifedipine>nitroglycerin >iproveratril>dipyridamole, prenylamine, lidoflazine, papaverine>carbochromene, trapymin>visnadin, khellin, which was to 1: 1/3: 1/10: 1/100: 1/300: 1/1000. These compounds caused a greater increase in the rate of coronary blood flow rather than changes in myocardial oxygen consumption but in a different grade, while isoprenaline caused a vasodilation paralleling an increase in myocardial oxygen consumption. Thus, the ratios of coronary blood flow v.s. myocardial oxygen consumption were approx. graded as follows; nitroglycerin, iproveratril, dipyridamole>nifedipine, lidoflazine, prenylamine, carbochromene, papaverine, visnadin>trapymin, khellin. It is concluded that the vascular smooth muscle of the coronary artery is mainly relaxed by the direct action of these drugs but partly by the indirect metabolic effect on the cardiac muscle. Different mechanisms of relaxation of the coronary artery lead to classification of coronary vasodilators into several different groups.
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Hidenori OHASHI, Akira OHGA, Koji SAITO
1973 Volume 23 Issue 4 Pages
467-477
Published: 1973
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Guinea-pig taenia colt suspended in a depolarizing solution without Ca responded to Ca by a contraction. The effects of adrenaline, noradrenaline and isoprenaline on the contractile response were investigated at 20°C and at 37°C. Contractile response to Ca was not significantly affected by adrenaline and noradrenaline, but was reduced by isoprenaline at 37°C. At 20°C, all the three catecholamines inhibited Ca-contraction. The potency in producing the inhibition was isoprenaline, adrenaline, noradrenaline, the same sequence of potency as related to beta-receptor mediated responses. Treatment with a beta-receptor blocking agent markedly reduced or abolished the inhibitory effects, and consequently the Ca-contraction was enhanced by adrenaline and noradrenaline at 37°C. Treatment with an alpha-receptor blocking agent increased the inhibitory effects so that adrenaline and noradrenaline reduced the Ca-contraction at 37°C as well as at 20°C. The order of potency in producing the inhibition after alpha-receptor blockade was again isoprenaline, adrenaline, noradrenaline. It was concluded that the stimulatory effect is mediated by alpha-receptor activation and the inhibitory effect by beta-receptor activation. After beta-receptor blockade and at 37°C, adrenaline and noradrenaline applied after Ca caused further development of tension. The contractile response to adrenaline resembles the slow component of the ACh-induced contraction, regarding time course and susceptibility to removal of Ca from the extracellular medium. Adrenaline enhanced the Ca-contraction to the same extent before and after frequent exposures to ACh to deplete cell-bound Ca. These findings suggest that the enhancement of the Ca-contraction by adrenaline and noradrenaline is dependent on increased permeation of Ca ions across the cell membrane.
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Hironori NAKANISHI, Hiroshi TAKEDA
1973 Volume 23 Issue 4 Pages
479-490
Published: 1973
Released on J-STAGE: December 19, 2006
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The study was designed to confirm the hypothesis that adenosine 5' triphosphate (ATP), in addition to Norepinephrine (NE) is involved in the excitatory transmission between the hypogastric nerve terminal and seminal vesicle in the guineapig. ATP produced a contraction in the isolated seminal vesicle. The pattern of contraction in response to exogenously administered ATP resembled that of nervemediated contraction in respect of short latency, rapid rising phase and short duration. The contractions in response to both post-ganglionic hypogastric nerve stimulation and exogenously administered ATP were remarkably enhanced in the presence of NE. The potentiating effect of NE on both responses was depressed with the pre-treatment of adrenergic α-blocking agents such as tolazoline, phenoxybenzamine, yohimbine and hydergine. The contractile responses to both hypogastric nerve stimulation and exogenously administered ATP were affected by pre-treatment with various adrenergic α-blocking agents; tolazoline augmented both responses; phenoxybenzamine had a variable effect on both responses; yohimbine and hydergine depressed both responses. The contractile response to NE was depressed or abolished by these adrenergic α-blocking agents. The contractile responses to both hypogastric nerve stimulation and exogenously administered ATP were also modified by cholinergic drugs; acetylcholine (ACh) enhanced both responses; physostigminc enhanced both responses as well as the response to ACh. Atropine slightly depressed both responses and abolished the response to ACh. Atropine also slightly depressed the nervemediated contraction in the reserpinized preparation. A relatively longer period of hypogastric nerve stimulation caused a biphasic contraction of the seminal vesicle. The initial “twitch” like contraction was resistant to reserpine-pretreatment, while the second slow rising contraction was abolished. The potentiating effect of NE on contractile responses to both hypogastric nerve stimulation and exogenously administered ATP was observed even in the reserpinized preparation. The sensitivity to NE was increased after denervation, while that to ATP was almost unaltered. The potentiating effect of NE on ATP-induced contraction was still observed in the denervated preparation. These findings are consistent with the hypothesis that ATP is involved in excitatory transmission between the hypogastric nerve and seminal vesicle in the guinea-pig. Possible role of ATP in the transmission-mechanism was discussed herein.
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Yasuo ENDO, Yasumi OGURA
1973 Volume 23 Issue 4 Pages
491-496
Published: 1973
Released on J-STAGE: December 19, 2006
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Metanephrine, adrenaline (together with tyramine and normetanephrine) and noradrenaline (together with dopamine) were separated by a simple chromatographic procedure on a phospho-cellulose column. The elution was carried out with 0.025M phosphate buffer (pH 6.2) containing EDTA. The method was successfully applied to neutralized perchloric acid extract of biological material. Separations of other amines (tryptamine, serotonin, histamine, agmatine, putrescine, cadaverine, spermidine and spermine) and basic amino acids (lysine, histidine and arginine) also were achieved utilizing the same column.
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Takeshi OSHIMA, Seiji KUMAKURA, Hiroyuki KOIKE, Koichi NAKAYAMA
1973 Volume 23 Issue 4 Pages
497-513
Published: 1973
Released on J-STAGE: December 19, 2006
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β-Adrenergic blocking activity and other pharmacological properties of CS-359, 5-methyl-8-(2-hydroxy-3-t-butylaminopropoxy) coumarin were compared with those of propranolol. CS-359 inhibited the positive chronotropic and the smooth muscle relaxing responses to isoproterenol. The cardiac effect of stellate ganglion stimulation in anesthetized dogs was also abolished. CS-359 given orally to conscious dogs inhibited the positive chronotropic response to isoproterenol given i.v. The β-adrenergic blocking activity of this compound was 2 to 3 times more potent than that of propranolol, both of which were devoid of any intrinsic stimulant activity. Aconitine and ouabain-induced arrhythmias in anesthetized dogs were protected by CS-359. As to local anesthetic action on frog sciatic nerve and guinea-pig cornea, CS-359 had one-tenth the activity of propranolol. Concerning percent reduction of the maximum rate of rise of action potential recorded intracellularly from the ventricular muscle fiber, CS-359 was 3 times less potent than propranolol. It reduced heart rate but had only minor effects on the blood pressure and respiration in anesthetized dogs. These data suggest that CS-359 is a more specific β-adrenergic blocking agent with a greater potency and a less cardiac depression than propranolol.
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II. PROPERTIES OF CYCLIC AMP DEPENDENT PROTEIN KINASES IN THE ADRENAL GLAND
Sumio SHIMA, Masayuki MITSUNAGA, Yoshiko KAWASHIMA, Shigeru TAGUCHI, T ...
1973 Volume 23 Issue 4 Pages
515-522
Published: 1973
Released on J-STAGE: December 19, 2006
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Studies on the zonal function of CAMP-binding protein (regulatory protein) and CAMP-dependent protein kinases in bovine adrenal glands have been made. Partially purified CAMP-binding protein from bovine adrenal gland divided into three zones, the capsular (zona glomerulosa), the decapsulated (zona fasciculata and reticularis) and the medulla gland was found in microsomal and cytosol fractions. The affinity and activity of the protein binding to CAMP from the cortex (the capsular, Ka, 4.7×10
-9 M ; activity, 4.6 p mole/mg protein, and the decapsulated, Ka, 4.2×10
-9 M; activity, 4.7 p mole/mg protein) was higher than from the medulla (Ka, 17×10
-9 M; activity, 2.2 p mole/mg protein). Two CAMP-dependent protein kinases, partly associated with CAMP-binding regulatory protein were partially purified from the cortex (the capsular and the decapsulated gland) and the medulla gland. The Km (8.6×10
-8 M) for CAMP of protein kinases from the cortex (the decapsulated gland) was lower than the Km (1.7×10
-7) from the medulla gland. Higher activity of CAMP-dependent protein kinases from the cortex than the medulla was discussed on the basis of differences in their regulatory proteins to which CAMP binds in an allosteric manner.
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Isamu YAMAGUCHI, Shoji KATSUKI, Takeo OHASHI, Shigenobu KUMADA
1973 Volume 23 Issue 4 Pages
523-534
Published: 1973
Released on J-STAGE: December 19, 2006
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Neuroleptics, antidepressants and minor tranquilizers were compared quantitatively for the effects on gastric secretion in Shay rats and on barbiturate sleep in mice. In this experiment, it was shown that these two actions of neuroleptics are clearly related and it is suggested that there may be some relationship between these two actions themselves regarding neuroleptics. The antisecretory action of neuroleptics and antidepressants, mentioned above, was reduced in rats pretreated with reserpine. The gastric secretion in Shay rats was clearly enhanced following a single injection of reserpine. This enhanced secretory volume and reduced antisecretory activity of chlorpromazine after reserpine returned to the control concomitantly with the recovery of the cerebral levels of norepinephrine and serotonin and gastric levels of norepinephrine. Antisecretory activity of imipramine and gastric levels of serotonin revealed a more rapid recovery after reserpine treatment. Furthermore, reserpine analogues and p-chlorophenylalanine were studied for the effects on the secretory volume and the antisecretory activity of chlorpromazine in Shay rats and on monoamine contents. It is postulated that the cerebral rather than gastric norepinephrine plays an inhibitory role in gastric secretion in Shay rats and is presumably involved in the antisecretory effect of chlorpromazine, and also possibly that of neuroleptics and antidepressants.
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Ryozo KOSHIURA, Hideo KATO, Takaaki MORI
1973 Volume 23 Issue 4 Pages
535-541
Published: 1973
Released on J-STAGE: December 19, 2006
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The antitumor activity of some 1, 2-bis(chloroalkyl)piperidine derivatives on Ehrlich ascites carcinoma cells was examined employing the in vitro-in vivo test method. The same compounds which have chloromethyl group in 2-position of the piperidine nucleus showed positive results. Among them, DL-1-β-chloroethyl-2chloromethylpiperidine hydrobromide (CAP-1) was found to be most effective in inhibiting the growth of tumor cells. Thus, CAP-1 was further investigated for the in vivo antitumor effect against certain rodent tumors. CAP-1 showed a remarkable prolongation of the survival time of mice bearing Ehrlich ascites carcinoma or sarcoma 180 when administrated i.p. a dose of 2-1 mg/kg/day for 7 consecutive days. This compound was also effective in inhibiting the growth of solid type of Ehrlich carcinoma. It has been observed that the average survival time of mice bearing mouse leukemia L1210 increased with i.p. administration of CAP-1 in doses ranging from 0.5 to 2 mg/kg/day for 7 days. CAP-1 was effective in prolonging the life-span of rats bearing Yoshida sarcoma or ascites hepatoma AH13 when given i.p. at a dose of 0.5-0.0625 mg/kg/day for 7 days.
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I. EFFECTS OF EPINEPHRINE AND ADRENERGIC BLOCKING AGENTS ON GLUCONEOGENESIS IN PERFUSED LIVER
Yasumichi HAGINO, Mitsuyoshi NAKASHIMA
1973 Volume 23 Issue 4 Pages
543-551
Published: 1973
Released on J-STAGE: December 19, 2006
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Gluconeogenesis from lactate in normal and hypothyroid rat liver was examined to clarify the adrenergic receptor mechanisms. When epinephrine was perfused into normal liver, the level of glucose in perfusate was elevated approx. 2fold. Hypothyroid liver also responded to epinephrine. In the normal liver, addition of an alpha or beta adrenergic blocking agent together with epinephrine did not show any significant change as compared to epinephrine alone, but, in hypothyroidism, a different metabolic response was observed with the administration of adrenergic antagonists together with epinephrine. Dibutyryl cAMP had the same effect as epinephrine on gluconeogenesis from lactate in both normal and hypothyroid livers.
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Tetsuyuki NASU, Norimoto URAKAWA
1973 Volume 23 Issue 4 Pages
553-561
Published: 1973
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The effect of cholinergic drugs on Ca movement was investigated in guinea pig taenia coli. In the presence of carbachol (1×10
-6 M), Ca content and extracellular space did not differ from control value,
45Ca uptake and efflux increased in the “early phase” and the size of cellular Ca fraction which did not exchange within 4 min (tightly bound fraction, TBF) increased in the “late phase” in the contraction. When the muscle was pretreated with atropine (1×10
-6 M), carbachol did not induce the contraction and 45Ca uptake and efflux in the “early phase” and the size of TBF in the “late phase” was maintained at the control value. The effect of pilocarpine (5×10
-6 M) and acetylcholine (1×10
-5 M) on Ca movement was the same with carbachol. In summary, cholinergic drugs increase Ca exchange and continuously accumulate the cytoplasmic Ca ions into the slow exchanging fraction. Changes in Ca movement by various stimulants were classified into three types, 1, increase in Ca exchange, 2, increase in Ca net influx and subsequent accumulation and 3, release of cellular Ca and subsequent accumulation.
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Isao WATANABE, Hiroshi SAITO, Keijiro TAKAGI
1973 Volume 23 Issue 4 Pages
563-571
Published: 1973
Released on J-STAGE: December 19, 2006
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Pharmacological properties of fractions obtained from Zizyphus seeds were estimated by a screening method consisting of 5 tests: 1) neuropharmacological observations in mice, 2) tests on the respiratory and cardiovascular systems in the rat, 3) tests on the isolated guinea pig ileum, 4) potentiation of hexobarbital anaesthesia, and 5) inhibition of writhing syndrome induced by acetic acid. Z. No. 2, Z. No. 3 and Z. No. 5 were confirmed to have sedative activity as a result of tests I and IV, and were estimated to have analgesic and anti-inflammatory properties from test V. Z. No. 5a was determined to have the strongest activities. The arterial blood pressure showed a prolonged elevation by fat and oil fractions, which was not eliminated by Phentolamine and hexamethonium. Water soluble fractions showed a transient hypotension, which was partially eliminated by atropine but not by diphenhydamine and propranolol. Increase of the contraction induced by nicotine could be seen in all fractions. Increase of the contraction induced by serotonin could be seen in fat and oil fractions. Water soluble fractions showed cholinergic activity. Papa-verine-like activity was noted in Z. No. 3.
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Issei TAKAYANAGI, Keijiro TAKAGI
1973 Volume 23 Issue 4 Pages
573-575
Published: 1973
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Takashi OCHIAI, Taku NAGAO, Sakae MURATA, Kenichi YOSHIMOTO, Yoshio KO ...
1973 Volume 23 Issue 4 Pages
575-578
Published: 1973
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Go KINOSHITA, Eiko SHIOHARA, Miyoko TSUKADA, Suehiro NAKANISHI
1973 Volume 23 Issue 4 Pages
578-580
Published: 1973
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Susumu SATOH, Norio TAIRA, Koroku HASHIMOTO
1973 Volume 23 Issue 4 Pages
581-583
Published: 1973
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Shoji MARUYAMA
1973 Volume 23 Issue 4 Pages
583-585
Published: 1973
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Wen-Hsiung LEE, Motohatsu FUJIWARA
1973 Volume 23 Issue 4 Pages
586-588
Published: 1973
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Sekizo KOJIMA, Masahiro IKEDA, Akira TSUJIMOTO
1973 Volume 23 Issue 4 Pages
588-591
Published: 1973
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Terumi NAKAJIMA, Shumpei SAKAKIBARA, Akira SAKUMA, Hirofumi SOKABE
1973 Volume 23 Issue 4 Pages
591-593
Published: 1973
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Masao KOIDA, Shigeru MURAOKA, Masakatsu TAKAHASHI, Hiroshi KANETO
1973 Volume 23 Issue 4 Pages
593-595
Published: 1973
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Mieko KIMURA, Yoshinori ITOKAWA, Chikako TANAKA
1973 Volume 23 Issue 4 Pages
595-597
Published: 1973
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