The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 15 , Issue 3
Showing 1-18 articles out of 18 articles from the selected issue
  • YOSHIHISA NAKAI, SHUJI TAKAORI, KIRO SHIMAMOTO
    1965 Volume 15 Issue 3 Pages 201-209
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It has been well-known that the electrical activity of the central nervous system is facilitated by relatively lower doses of central depressants. Many reports were presented to support the facilitatory mechanism in the brain of exprimental animals at lower dose levels of barbiturates: lowering of stimulation threshold for the recruiting response by King (1) and' Domino (2), increase in amplitude of the somatosensory evoked potential recorded from the internal capsule by King et al. (3), and increase in amplitude of the evoked potential recorded from the auditory cortex by Pradhan and Galambos (4). Nakai (5) and Nakai and Takaori (6) showed that pentobarbital sodium, chloralose and chlorpromazine increased the magnitude of the cortical potential evoked by click stimuli and accelerated the manifestation of the ensuing rhythmic after-discharges, while urethane and ethyl alcohol even in small doses reduced the amplitude of the evoked potential.
    The role of the inferior colliculus as a relay nucleus for the auditory pathway was investigated electrophysiologically by Ades and Brookhart (7) and Thurlow et al. (8). However, there is scarcely any systematic study concerning the effects of central depressants on the evoked potential in the inferior colliculus. It is considered that the effect of central depressants on the collicular acoustic potential may differ from that on the cortical one. The difference may give some clue for the elucidation of the central auditory mechanism.
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  • YOSHIMI MISU, SHUJI TAKAORI, KIRO SHIMAMOTO
    1965 Volume 15 Issue 3 Pages 210-216
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The cholinergic effect of carnitine (β-hydroxy, γ-trimethylammonium butyrate) on the cardiovascular and digestive systems has been well-established by several investigators (1-8). Recently, physiological existence of carnitine in the heart muscle has attracted notice and carnitine has been regarded as a heart hormone which may contribute to regulate the contraction of the heart muscle and the coronary flow. The addition of carnitine to an incubation medium resulted in enhanced oxidation of long-chain fatty acids by heart muscle preparation (9) as well as by liver slices and homogenates (10, 11) and skeletal muscle particulates (12). Fritz et al. (9) showed that the activity of carnitine derivatives required to enhance fatty degradation was abolished by replacement of the carboxyl group with an ester grouping. Furthermore, Fritz and Yue (13) demonstrated that carnitine enhanced the conversion of acetyl-CoA to CO2 and augmented oxygen consumption by heart muscle mitochondria when acetyl-CoA was the substrate. Acetylcarnitine decreased the carnitine enhancement of acetyl-CoA conversion to CO2, via operation of the carnitine acetyltransferase reaction: acetyl-CoA+ carnitine⇔acetylcarnitine+CoA. They concluded that carnitine acetyltransferase and carnitine might function as a shuttle system to facilitate acetylgroup movement across the mitochondria membrane.
    The present experiments were therefore designed to study the effects of carnitine and its methylester on the spontaneous contraction and the transmembrane potential in the isolated rabbit's atrium as a preliminary investigation to correlate the pharmacodynamic effects of carnitine on the heart with the above-mentioned biochemical effects.
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  • II. SECRETORY RESPONSE OF THE ADRENAL MEDULLA TO ACETALDEHYDE: EXPERIMENT WITH THE PERFUSED CAT ADRENALS
    JIRO AKABANE, SUEHIRO NAKANISHI, HIROSHI KOHEI, SUSUMU ASAKAWA, RIICHI ...
    1965 Volume 15 Issue 3 Pages 217-222
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In the previous paper (1), we have shown that acetaldehyde released catecholamines from store sites located in or near the nerve terminals as well as from the adrenal medulla, and the action of acetaldehyde on the adrenal medulla was blocked by neither hexamethonium nor atropine.
    In the present paper, we have dealt with the secretory response of adrenal medulla to acetaldehyde in the perfused cat adrenals, in the hope of gaining further insight into its mechanism.
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  • TSUTOMU SAKURAI, YUICHI HASHIMOTO
    1965 Volume 15 Issue 3 Pages 223-233
    Published: September 01, 1965
    Released: February 02, 2007
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    In study of the mechanism of renal hypertension, attention has been concentrated on investigation of the role of neurogenic component. Several reports (1-3) have suggested that there are some relations between action of angiotensin and function of the sympathetic nerve endings. Lewis (3) suggested that the action of angiotensin on the vessel wall may result from local release of catecholamine from the sympathetic nerve endings. McCubbin and Page (2) found that infusion of angiotensin caused marked enhancement of the cardiovascular response to agents and procedures causing the release of endogenous noradrenaline.
    The present experiments were undertaken primarily to examine whether the adrenergic mechanism is involved in the process of the vasoconstrictor action of angiotensin. In these experiments isolated rabbit ear vessels were perfused. The second object of the experiments was to test whether release of noradrenaline from sympathetic nerve endings could be augmented during the infusion of angiotensin which causes an elevation of the blood pressure. For this study, urinary catecholamine and their orthomethylated products were measured after the infusion of angiotensin. Tyramine which causes release of noradrenaline from sympathetic nerve endings was used to study the functional state of the sympathetic nerve endings.
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  • NOBORU TODA, MOTOHATSU FUJIWARA, KEISUKE HATTORI
    1965 Volume 15 Issue 3 Pages 234-243
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The previous reports from this laboratory (1-4) have shown that reserpine in a concentration of 10-5 g/ml results in a decrease in the amplitude and prolongation of depolarization and repolarization phases of transmembrane action potential and sometimes an arrest of rhythmic contraction in the isolated rabbit atria. The finding that noradrenaline restarts the atrial beat which has been arrested by reserpine led us to the assumption that endogenous noradrenaline may play an important role in the intrinsic rhythmicity of the heart. However, there has been presented evidence against this assumption (5, 6). The arrested atria can be restarted by noradrenaline without significant increase in the level of tissue noradrenaline. By contrast, the atria from the rabbit pretreated with reserpine and depleted of noradrenaline continue to contract long after isolation. Consequently, it has been postulated that the cardiac inhibitory effects of reserpine in vitro do not derive from a decrease in the amount of endogenous catecholamines but from some direct action of unknown mechanism (4).
    In the course of experiments studying the effects of adrenergic drugs on the atrial response to stimulation of the vagus nerve, Toda et al. (7) have found that a deficiency of oxygen supply results in a potentiation of the vagal response without modifying acetylcholine response and this is similar to that of reserpine. Reserpine reduces oxygen consumption of the isolated rabbit intestine (8) and the rat brain homogenate as well as liver and kidney slices (9). The present experiments were designed to ascertain whether a close relationship exists between the cardiac inhibitory effect and the depression of tissue respiration following reserpine in vitro.
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  • KATSUYA IWATSUBO
    1965 Volume 15 Issue 3 Pages 244-256
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The drug-metabolizing enzymes catalyzing such reactions as oxidation, reduction, conjugation and hydrolysis have been reported to be localized mainly in liver microsomes (1, 2). Microsomes may also be considered as hydrolytic particles (3). The enzymes hydrolyzing ester-form drugs, e.g. aspirin (4-6), procaine (7), cocaine (8-11), atropine (8, 12, 13) and choline-esters (14, 15) have also been shown to be in the liver and some other tissues, but little is known 'about the properties and intracellular localization of these esterases as compared with cholinesterase which is closely related to synaptic transmission. It appears of interest to investigate drug-metabolizing enzymes in liver microsomes further to elucidate their pharmacological actions and mechanisms of detoxication.
    As a fundamental classification of esterases, Aldridge (16) showed that 10-5 M organophosphorous compounds inhibit many enzymes possessing carboxylic esterase activity while other esterases are unaffected. He has named the latter A-type and the former B-type esterase. Neither A nor B-type are sensitive to 10-5 M eserine. Cholinesterase is inhibited completely both by 10-6 M organophosphates and by 10-5 M eserine. Subsequently A and B-types and cholinesterase in many vertebrate plasmata were separated electrophoretically by Goutier (17) and Augustinsson (18). Microsomal esterases have not been examined with this technique.
    The present paper describes experiments on the classification of esterases, especially drug-hydrolyzing enzymes, in liver microsomes of some rodents. The microsomes “solubilized” with sodium deoxycholate were fractionated chromatographically or electrophoretically, and the sensitivities of the esterases in each fraction to inhibitors and their kinetics were investigated.
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  • YOSHIMI MISU, SHUJI TAKAORI, KIRO SHIMAMOTO
    1965 Volume 15 Issue 3 Pages 257-266
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Since the role of thiamine pyrophosphate in the metabolism of α-keto acids has been biochemically established, many investigations have been devoted to understand its biological activity on the enzymatic mechanism. Recently, various derivatives of thiamine have been synthesized and found to be active in several enzyme systems in the brain, peripheral nerve, heart and liver (1-3).
    On the other hand, it has been reported that thiamine in higher concentration produces a negative inotropic effect in the isolated heart of the turtle and the heartlung preparation of the dog as well as in the isolated atrium of the cat (4, 5). The synthesis of alkyldisulfide and carboethoxy derivatives of thiamine and their wide clinical uses in comparatively large doses prompted the re-examination of the pharmacological contribution of thiamine for the clinical indications. More recently, it has been demonstrated that these derivatives in higher concentration produce a positive inotropic effect on the isolated atrium of the guinea pig (6, 7) and restore the cardiac depression caused by a variety of carbohydrate metabolic inhibitors (8, 9), and that thiamine and its derivatives prolong the repolarization time of the atrial action potential in the guinea pig (7).
    It has been speculated that the cardiac cholinergic nerve liberates thiamine when it is activated, and thiamine plays an essential role in the maintenance of the physiological function of the peripheral nervous system (1), and that thiamine may be an inhibitor of cholinesterase activity (10). Moreover, it has been reported that thiamine derivatives produce blocking effects on the sympathetic ganglion (11) and the neuro-muscular junction (12).
    In the present paper, the effects of thiamine hydrochloride and its derivatives on the spontaneous contraction and the transmembrane potentials of the isolated atria of the rabbit were investigated in an attempt to know the relationship between their pharmacodynamic effects and biochemical ones.
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  • JIRO SUGIMOTO, NAOTAKE IIDA
    1965 Volume 15 Issue 3 Pages 267-273
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It is generally accepted that the remarkable effect of digitalis on heart falure is caused by its specific action on the contractile mechanism of the heart muscle. The mode of pharmacological action of digitalis glycosides have been studied by many investigators, and it has been claimed that digitalis might have some influence on the energy production mechanism of the heart. The metabolic pathway of heart muscle contraction is not positively influenced by digitalis glycosides, though they do bring about an increase in contractile force [Wollenberger (1), Bing et al. (2, 3)]. Szent-Györgyi (4) reported that actomyosin is influenced by ATP and inorganic ions but not by digitalis. However, it has been reported that ATP-ase activity in the muscle cell membrane of rat hearts is promoted by digitalis in therapeutic dosage [Repke (5)]. On the other hand, Hadju and Szent-Györgyi (6) reported that the decrease in K-ion concentrations in the heart muscle induces an increase in contraction, and digitalis augments an efflux of the K-ions in the heart muscle. On contrary, Klaus et al. (7) reported that the influx of 42K-ions into the heart muscle cells was increased by digitalis in therapeutic doses. The cardiac action of digitalis has been explained by some investigators as that of an autonomic drug due to the result that digitalis increases adrenaline action [Donielpolu (8), Fujita (9)].
    Our experiment were carried out to discover the relation of digitalis action to endogenous catecholamine mobilization in the atria from the standpoint that the catecholamines in heart muscle are mostly in a bound form and the contractile function of heart is controlled by the released catecholamine available.
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  • MOTOHATSU FUJIWARA, TAKASHI HONJO, NOBORU TODA, KIRO SHIMAMOTO
    1965 Volume 15 Issue 3 Pages 274-279
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Previous reports from this laboratory have indicated that reserpine inhibits and eventually abolishes rhythmic contractions of isolated rabbit atria despite only 20% decrease in norepinephrine levels, whereas atria from rabbits pretreated with reserpine in vivo and depleted of norepinephrine continue to contract long after isolation (1-4). The ability of reserpine to release serotonin in vitro is highly dependent upon temperature (5). On the other hand, the release of adrenal catecholamines following reserpine is mediated at least in part by activity of the sympathetic nervous system (6, 7). Thus it is possible that the slight decrease in atrial norepinephrine levels caused by reserpine in vitro is due to low environmental temperature and/or no impingement of nerve impulses on the pacemaker area of the isolated atrial preparation.
    The primary aim of this study, was to determine whether altering the temperature of bath fluid and electrical stimulation of the pacemaker area promote the release of atrial norepinephrine by reserpine in vitro. The results show that modifications in experimental conditions do not result in a promotion of the norepinephrine release due to reserpine and that reserpine in vitro releases norepinephrine via a mechanism different from that of catecholamine depleting agents acting in vivo, such as reserpine and guanethidine.
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  • YOSHITSUGU OSUMI
    1965 Volume 15 Issue 3 Pages 280-294
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Though the exact pathogenesis of clinical arteriosclerosis remains still to be settled, experimental atheromatosis in animals such as rats, rabbits, dogs, monkeys and birds caused by cholesterol feeding with or without addition of cholic acids and vegetable or animal oil has widely been available for resolving this problem. Recently, Takaori and Shimamoto (1) and Takaori, Osumi and Shimamoto (2) in this laboratory have shown that the mode of formation of cholesterolemia and cholesterol deposition in the tissues produced by cholesterol feeding markedly differs in rats and rabbits. They have further shown that though hypercholesterolemia and cholesterol deposition in rats spontaneously subside despite the continuation of the cholesterol feeding, spontaneous declination during the feeding term is never observed in rabbits.
    The lowering effect of thyroactive substances on the elevated level of the serum and tissue cholesterol in the experimental animals has been demonstrated in chickens (3, 4), rats (5) and rabbits (6, 7). Takaori, Osumi and Shimamoto (2) have shown that the administration of 3, 5, 3'-triiodo-4-acetyl-thyroformic acid (TBF-43), a possible metabolite of thyronine, does prompt the spontaneous declination of hypercholesterolemia and cholesterol deposition in the rats, and that the same procedure in the rabbits is almost non-effective, though the subcutaneous fatty tissues are much reduced. In the current report it was attempted to determine whether 3, 5, 3'-triiodothyronine (T3) had similar effects on cholesterolemia and cholesterol deposition compared with TBF-43, and whether the effect, if any, correlated with the lipolytic or thyrotropic mechanism of the compound.
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  • JIRO NAKANO
    1965 Volume 15 Issue 3 Pages 295-297
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Acute anoxic conditions as seen frequently in circulatory and respiratory failures are almost always associated with release of catecholamines from the sympathetic nerve endings and/or adrenal medullas (1, 2). It has been known that catecholamines inhibit the intestinal motility of the isolated rabbit ileum (3-7), whereas anoxia increases the motility before complete paralysis (8-11). The present study was undertaken to investigate the effect of anoxia on the intestinal motility response to norepinephrine in the isolated rabbit ileum.
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  • IWAO YAMAMOTO, KIHEI OTORI, SEKIZO KOJIMA, KOJI MIZOGUCHI
    1965 Volume 15 Issue 3 Pages 298-309
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In the course of investigation of antagonistic actions of thiamine against nicotine, Yamamoto and his co-workers led to a conclusion that a main antagonistic site in the peripheral region is the nervous ganglion and the antagonistic action is involved in the competition at the receptor site (1-6). The antagonism between nicotine and thiamine dealt with the investigation was by no means referable to the action of thiamine as a vitamin. In its thiazole ring structure thiamine has a quaternary ammonium, as other ganglion blockers have. The ganglion blocking action of thiamine on the cat's nictitating membrane has been previously demonstrated by Yamamoto and his co-workers (3-6) and Mazzella et al. (7). The present investigation was undertaken to compare the pharmacological properties of thiamine and its related compounds with those of hexamethonium and tetraethylammonium with special reference to the ganglion blocking activity.
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  • MOTOHATSU FUJIWARA, GEORGE NAKATANI, NOBORU TODA
    1965 Volume 15 Issue 3 Pages 310-316
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The increase in myocardial contractile force after administration of epinephrine is closely related to the activation of cyclic 3', 5'-AMP with a subsequent conversion of phosphorylase b to a (1-5). Further, it seems likely that there exists a close relationship between the level of circulating catecholamine and the activity of phosphorylase in the heart, based on the finding that the injection of ganglionic stimulating agents produces the simultaneous increase in myocardial contractile force and augmentation of phosphorylase activity (6). The observation of Nakatani (7) that physostigmine augments phosphorylase activity in the heart and this augmentation is prevented by prior reserpine is compatible with the view that endogenously liberated catecholamines increase phosphorylase a.
    However, there are controversial reports regarding the effect of reserpine on heart phosphorylase activity: no significant change (3, 8), increase (5) and decrease (9), and there is no conclusive evidence that reserpine decreases heart phosphorylase. This is incompatible with the concept that there is a positive correlation between the amount of endogenous catecholamines and heart phosphorylase a activity. All these expriments, however, were conducted in the in situ preparations. To our knowledge, the one exceptional observation was made by Giotti (10), who reported insignificant effects of reserpine in vitro on phosphorylase activity in guinea pig atria.
    The present study was undertaken to investigate the relationship between reserpine and phosphorylase activity in the isolated rabbit atria.
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  • YUICHI HASHIMOTO
    1965 Volume 15 Issue 3 Pages 317-319
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    During hemorrhagic hypotension in dogs, plasma catecholamine level was found to be elevated due to increased secretion of catecholamine from the sympathoadrenal system (1, 2). In rabbits, depletion of norepinephrine and increment of epinephrine in the left ventricle were observed after prolonged hemorrhagic hypotension, and the correlation of myocardial norepinephrine and cardiac performance was suggested (3). On the other hand, metabolic disturbances in shock state were also much discussed (4, 5). Therefore, it seems to be interesting to investigate how elevated plasma catecholamine changes myocardial catecholamine level, and whether prolonged hemorrhagic hypotension induces certain changes to the myocardial norepinephrine synthesis.
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  • YUICHI HASHIMOTO, YOSHIHIRO OHI, HIROSHI YOSHIDA, REIJI IMAIZUMI
    1965 Volume 15 Issue 3 Pages 320
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • AKIRA SAKUMA
    1965 Volume 15 Issue 3 Pages 321-322
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • R.C. SRIMAL, K.D. JAITLY, K.P. BHARGAVA
    1965 Volume 15 Issue 3 Pages 322-324
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • YUICHI HASHIMOTO, YOSHIHIRO OHI, REIJI IMAIZUMI
    1965 Volume 15 Issue 3 Pages 324-325
    Published: September 01, 1965
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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