The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 20 , Issue 4
Showing 1-22 articles out of 22 articles from the selected issue
  • K.M. DHASMANA, G.P. GUPTA, K.P. BHARGAVA
    1970 Volume 20 Issue 4 Pages 461-466
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    As early as 1906 Dale (1) reported that adrenaline causes relaxation of detrusor muscle and contraction of the vesical sphincter. However, the response of ureter to sympathomimetic amines is indefinite; some experiments indicate that the motility and tone of the ureter are lessened (2) while in the rabbit Ahlquist (3) observed a stimulant effect of the amines on the ureter. A similar effect was observed on the isolated ureters of buffalo (4), dog and pig (5-8). Ergotamine has been shown to block the stimulant effect of adrenaline on the vesical sphincter (1) but it does not block the inhibitory effect on the detrusor muscle (1). The ergotamine block indicates that the effect of adrenaline on the vesical sphincter was mediated through the alpha adrenergic receptors and the effect on the detrusor muscle could be through the beta receptors (3). Furthermore, on the basis of relative potencies of different sympathomimetic amines, Ahlquist (3) proposed alpha adrenergic receptors for the stimulant action on the ureter. The use of beta receptor blocking agent, dichloroisopropyl noradrenaline (DCI) has helped in demonstrating the presence of beta receptors in various tissues (9). The existence of beta receptors in the urinary bladder of cat has been recently demonstrated (10). The present work was undertaken to analyse the adrenergic receptors in the ureter, detrusor muscle and vesical sphincter of dog with the help of alpha as well as beta receptor blocking agents.
    Download PDF (301K)
  • N. SINGH, R.K. SRIVASTAVA, V.K. KULSHRESTHA, J.N. SINHA, R.P. KOHLI, K ...
    1970 Volume 20 Issue 4 Pages 467-472
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Since the introduction of dichloro analogue of isoprenaline (DCI) by Powell and Slatter (1), several β-receptor blocking agents have been introduced in the present day medicine. Among these, propranolol is being used in various clinical conditions like angina pectoris (2-3), myocardial infarction (4) and ventricular arrhythmias (5-6). Further, propranolol has been used as local anaesthetic in minor surgical procedures (7). However, the clinical usefulness of these agents in various cardiac conditions is limited by the fact that they, some times, induce severe and irreversible cardiac failure. The present study has been done on the heart-lung preparation of the dog with a view to assess the relative myocardial depressant activity of INPEA and propranolol and also to find out some suitable agents which may effectively antagonize the cardiac failure caused by these agents.
    Download PDF (288K)
  • KIYOSHI IMAI, YUZO HAYASHI
    1970 Volume 20 Issue 4 Pages 473-481
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It has been reported that administration of orally-active steroids such as norethandrolone (1, 2), norethisterone (3), methyltestosterone (4) and methandienone (5) can cause in some patients a type of cholestatic jaundice characterized by accumulation of bile in the liver without extrahepatic biliary obstruction (intrahepatic cholestasis), occurence of canalicular bile-plugs, absence of either parenchymal necrosis or portal inflammation, and an elevation of conjugated bilirubin in the serum. In addition, Schaffner and Popper (6) have shown that ultrastructural alterations of the liver comprizing a widespread dilatation of the biliary canaliculi and distortion of the canalicular microvilli are invariably associated with the intrahepatic cholestasis.
    Several authors have reported experimental studies in relation to the cholestatic effect of steroids. Schaffner and Popper (6) have demonstrated the occurence of canalicular dilatation in the liver of rats following administration of norethandrolone. Retardation of bromosulphalein excretion is known to occur in animals treated with methyltestosterone and norethandrolone (7-9). However, the experimental model with definite manifestations of intrahepatic bile-stasis such as conjugated hyperbilirubinemia or canalicular bile-plugs has not been established.
    In the course of studying the acute toxicity of norethisterone, 17α-ethinyl-19-nortestosterone, we found a consistent appearance of jaundice in DS mice following administration of a large amount of norethisterone as well as other C17 α-alkyl or alkynyl substituted steroids. This experiment attempted to evaluate the pathological entities of the norethisterone-induced jaundice in mice in comparison with the intrahepatic cholestasis in men caused by various steriod drugs.
    Download PDF (755K)
  • S.M. SHANBHAG, H J. KULKARNI, B.B. GAITONDE
    1970 Volume 20 Issue 4 Pages 482-487
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The alkaloid, berberine is widely distributed in the vegetable kingdom. The berberine containing plants are largely used in indigenous medicine. A crude extract known as “Rasaut, Rasvanti and Rasanjana” is a widely used household remedy as a stomachic, bitter tonic and diaphoretic. There is a renewed interest in berberine because of its reported usefulness in diarrhoeas (1) cholera (2) and experimental amoebiasis (3, 4). Some of our studies on the actions of berberine on the central nervous system are presented in this paper.
    Download PDF (325K)
  • HEITAROH IWATA, TOSHIHIRO DOHI, ITARU YAMAMOTO
    1970 Volume 20 Issue 4 Pages 488-496
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Siegmund et al. (1), Hendershot and Forsaith (2) and Vander Wende and Margolin (3) first described a syndrome, commonly referred to as “writhing”, which was induced in rodents by the intraperitoneal injection of various chemical agents. Collier et al. (4) have recently reported experiments on the abilities of various substances, including some occurring in tissues and causing pain in man, to induce abdominal construction in mice.
    Many investigators have described the non-specificity of the writhing syndrome, this phenomenon being blocked or antagonized by non-narcotic, and narcotic antagonists as well as narcotic analgesics. The inhibition of drug-induced writhing in mice has been proposed as a screening test for analgesics (1, 2, 5-7), although non-analgesic drugs also inhibit writhing (2, 8, 9).
    In the present experiments, intraperitoneal injection of the diazonium compound, 4 (or 5)-diazoimidazole-5 (or 4)-carboxamide had a profound effect on body temperature and induced the writhing syndrome. Both the severe hypothermia and writhing following its inejction could be ameliorated with analgesics. The mechanism on these effect are discussed.
    Download PDF (426K)
  • KEIJIRO TAKAGI, ISSEI TAKAYANAGI, TETSUYA KUDO, SATOSHI ISHIKAWA, MAKO ...
    1970 Volume 20 Issue 4 Pages 497-503
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    There have been some articles in regard to the pharmacological study on the extraocular muscles. Katz and Eakins (1) reported the in situ effect of drugs on electrically stimulated extraocular muscle of cats, and Kern (2, 3) studied the effect of sympathomimetic amines on the isolated extraocular muscles.
    However, there has been no publication, to our knowledge, in regard to the electrical stimulation of the isolated extraocular muscle-nerve preparations. The investigations on the neuromuscular junction in the extraocular muscle were generally carried out in the in situ experiments. In the in situ experiments a part of responses of the extraocular muscles to drugs may be due to secondary effects accompanied with responses of the intraocular muscles to the drugs. In the present study, the effects of drugs on the electrically stimulated extraocular muscle-nerve preparations isolated from rabbits were investigated and were compared with actions of the drugs in the in situ experiments. Furthermore, actions of drugs on the isolated extraocular muscles were examined.
    Download PDF (336K)
  • KEIJIRO TAKAGI, ISSEI TAKAYANAGI, YOSHIO KAZIWARA, YOSHIO HIRAMATSU, A ...
    1970 Volume 20 Issue 4 Pages 504-508
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    The concept of two adrenergic receptor mechanisms or α- and β-adrenergic receptor systems, originally proposed by Ahlquist (1) was based on orders of potency of a series of catecholamines. Since dichloroisoprenaline (DCI) was introduced as a new category of drugs that selectively blocked the response due to β-adrenergic activation, several β-adrenergic blockers were found. In this paper 2-(2-hydroxy-3-tert-butylaminopropoxy) chlorobenzene hydrochloride (D-69-12) has been found to be a potent β-adrenergic blocker. However, D-69-12 in very high concentrations relaxed the smooth muscle preparations. So mode of action of D-69-12 was examined. Furthermore, the dual action of D-69-12 on the smooth muscle preparations has been discussed in this paper.
    Download PDF (175K)
  • AKINOBU NAGAOKA, HISANORI KAWAJI, YOSHIO IMAI, HIROSHI FUKUI
    1970 Volume 20 Issue 4 Pages 509-516
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In 1963 Okamoto and Aoki (1) had separated, by selective inbreeding, a colony of Wistar rat with 100% incidence of spontaneous hypertension. These rats were named spontaneously hypertensive rats (SH. rats) and, thereafter, various investigations of these SH. rats have been carried out by Okamoto et al. Although this SH. rat was distributed to many other laboratories in Japan as well as in other countries, the accurate longevity and motal causes of the SH. rats remain still to be reported. Because of high incidence of pulmonary and other infections in the conventional circumstances, many rats died in early age accidentally. These interfered seriously with the studies on the sequences of developments of hypertension and its pathophysiological etiology. The present work revealed that the maintenance of the SH. rats in the specific pathogen free (SPF) condition prevented the animals from the infections and brought about the exact observation of the causes of the spontaneous death and of the hypertensive lesions at the advanced ages.
    Download PDF (524K)
  • NOBORU TODA, YOSHIHIDE YAMASAKI, MOTOHATSU FUJIWARA
    1970 Volume 20 Issue 4 Pages 517-529
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It is widely known that cardiac noradrenaline is markedly depleted by pretreatment of animals with reserpine (1) but only slightly reduced by treatment of the isolated heart with reserpine (2, 3). Pretreatment of animals with reserpine depresses the retention of exogenous noradrenaline in the heart (4) by reducing the uptake of the amine by storage granules (5) and by increasing the destruction of the amine by monoamine oxidase in sympathetic nerve terminals (6). Reserpine when applied in vitro significantly inhibits the uptake of the amine by the isolated heart (7). Reserpine is shown to disappear almost completely from the body in a few hours when injected intravenously (8) but when applied in vitro it acts directly on the heart until the drug is washed out repeatedly. Modification by reserpine of the cardiac functions and the responsiveness of the isolated heart to endogenous and exogeneous noradrenaline would be attributed to the marked depletion of cardiac noradrenaline, the inhibition of the amine uptake by the heart and/ or the actions of reserpine per se. Although the positive chronotropic response of the heart to sympathetic nerve stimulation and to indirectly-acting sympathomimetic amines is markedly reduced and the response to noradrenaline is enhanced by pretreatment with reserpine, little is known about the effects of reserpine applied in vitro on the responses to endogenous and exogeneous noradrenaline.
    The present investigation was undertaken to examine (a) effects of reserpine applied in vitro on the chronotropic response of isolated atria to sympathetic nerve stimulation, tyramine and exogenous noradrenaline, (b) modification of the contractile tension-frequency relationship and of the chronotropic and inotropic effects of noradrenaline by pretreatment of animals with reserpine, and (c) effects of treatment with noradrenaline or dopamine in the presence of monoamine oxidase inhibitor on the chronotropic response of atria from reserpine-pretreated rabbits to tyramine and to sympathetic nerve stimulation.
    Download PDF (575K)
  • HIDEAKI KARAKI, MIYOSHI IKEDA, NORIMOTO URAKAWA
    1970 Volume 20 Issue 4 Pages 530-535
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Previous studies have shown that Ca influx increased but Ca efflux did not change during the contracture of taenia coli induced in hypertonically added 40 mM potassium solution (1) and the results were supported by the others (2-6). Further, the movements of Ca in the muscle in high-K solution might be differently affected by ouabain and 2, 4-dinitrophenol during the abolition of the tonic tension by them (6, 7). The experiments reported here were carried out in purpose to find the nature of Ca distribution and exchange in guinea pig taenia coli in high-K solution using ouabain and 2, 4-dinitrophenol.
    Download PDF (258K)
  • SHIRO MORIMOTO, KENJIRO YAMAMOTO, KUNISUKE HORIUCHI, HIROSHI TANAKA, J ...
    1970 Volume 20 Issue 4 Pages 536-545
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    A release of renin from kidney cortex slices in vitro was first reported by the present authors (1). Recently, the renin release from kidney slices of rats, pretreated with deoxycorticosterone acetate, clipping of renal artery, bleeding or decapitation, was shown by Jong (2) and BOZOVIC et al. (3). In their experiments, the fundamental process of renin release has not been made clear. In our previous paper, it was pointed out that renin is released from dog kidney slices into an incubation medium depending on the temperature and pH of the medium and about 10% of renin contained in the original slices is released within 60 minutes of incubation.
    Presently, the effects of metal ions in the incubation medium and atmosphere on renin release were studied. From the present findings, it is assumed that renin is released, partialy included in the renin granule, into the incubation medium. Further study was made on the release of several enzymes found in other cell particles to compare the releasing pattern of renin from slices.
    Download PDF (414K)
  • (I) THE ACTIVITY OF DRUG-METABOLIZING ENZYMES AND ELECTRON TRANSPORT SYSTEM
    RYUICHI KATO, KIN-ICHI ONODA, AKIRA TAKANAKA
    1970 Volume 20 Issue 4 Pages 546-553
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In previous papers, it was reported that the activity of drug-metabolizing enzymes of liver microsomes was decreased in alloxan diabetic or fasted male rats (1, 2). The hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes were decreased in these animals, but the aniline and zoxazolamine hydroxylations were not decreased. In contrast to the results obtained with male rats, the hexobarbital hydroxylation and aminopyrine N-demethylation were not decreased in the microsomes from female rats. These results thus appeared to be related to the fact that the hexobarbital hydroxylation and aminopyrine N-demethylation are markedly stimulated by androgen, whereas the aniline and zoxazolamine hydroxylations are not stimulated (1, 2). From these results and others, it has been supposed that the decrease in the hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes from alloxan diabetic or fasted male rats is due to an impairment of the mechanism of androgen-dependent stimulation for these oxidative activities (1, 2).
    On the other hand, the hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes of mice and rabbits were not stimulated by androgen, and the lack of the androgen-dependent stimulating mechanism for the drug-metabolizing enzymes has been suggested (3, 4). Therefore, it is reasonable to speculate that, if the decrease in the hexobarbital hydroxylation and aminopyrine N-demethylation by the microsomes from alloxan diabetic or fasted male rats is due to an impairment of the androgen-dependent stimulating mechanism, the decrease in the oxidative activity does not occur in male mice and rabbits and that the sex difference in the alteration of drugmetabolizing enzymes due to alloxan diabetes or starvation is not observed in the liver microsomes from mice and rabbits.
    In the present studies, these possibilities were investigated through comparative studies on the effect of alloxan diabetes and starvation on the liver microsomes of both sexs of rats, mice and rabbits.
    Download PDF (347K)
  • (II) THE SUBSTRATE INTERACTION WITH CYTOCHROME P-450 IN DRUG OXIDATION
    RYUICHI KATO, KIN-ICHI ONODA, AKIRA TAKANAKA
    1970 Volume 20 Issue 4 Pages 554-561
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Imai and Sato (1), and Schenkman et al. (2) showed that a number of drugs which are substrates of hepatic microsomal monooxygenase react with a microsomal cytochrome called cytochrome P-450 to give characteristic types of spectral change. These results have suggested that the spectral changes observed are indicative of substrate interaction for enzymic hydroxylation (2) and that the magnitude of the substrate binding with cytochrome P-450 is one of important factors controlling the rate of the over-all hydroxylation of drugs by liver microsomes (3-6).
    In the preceding paper (7), it was demonstrated that, in contrast to the results obtained with male rats, the hexobarbital hydroxylation by liver microsomes was not decreased in alloxan diabetic or fasted male mice and rabbits. These results supported the hypothesis that the decrease in the hexobarbital hydroxylation in alloxan diabetic or fasted rats is due to an impairment of the androgen-dependent stimulating mechanism for drug-metabolizing enzymes (8, 9). It has been reported that the magnitude of hexobarbital-induced spectral change was greater in male rats than in the females, and that androgen administration increased the magnitude of the spectral change (3, 6). On the other hand, there was no clear sex difference in the magnitude of hexobarbital-induced spectral change in liver microsomes from mice and rabbits and the administration of androgen did not stimulate the magnitude of the spectral change (6, 10).
    In the present studies, therefore, the effect of alloxan diabetes or starvation on the binding of cytochrome P-450 with substrate in liver microsomes of both sexes of rats, mice and rabbits was investigated in relation to the effect on the hydroxylating activity for hexobarbital and aniline.
    Download PDF (359K)
  • RYUICHI KATO, KIN-ICHI ONODA, AKIRA TAKANAKA
    1970 Volume 20 Issue 4 Pages 562-571
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It is well documented that there is clear relationship between the rate of drug metabolism by liver microsomes and the intensity of the effect and toxicity of a variety of drugs (1-5). Recent studies indicated that the individual, strain, sex and species differences in the rate of drug metabolism appear to be factors responsible for the individual, strain, sex and species differences in the effect and toxicity of a variety of drugs (2, 3, 6, 7). Jay (8) observed marked difference in the duration of hexobarbital anesthesia in mice of various strain and later Quinn et al. (2) studied the strain difference in the metabolism of hexobarbital by liver microsomes from different strain of rats.
    In the present communication, strain differences of rats and mice used commonly in Japan concerning the activity of microsomal drug-metabolizing enzymes were studied in relation to the effect and toxicity of drugs. Thus the studies on the nature of strain difference in the drug effect and toxicity are important for the evaluation of drug action.
    Download PDF (385K)
  • RYUICHI KATO, AKIRA TAKANAKA, KIN-ICHI ONODA
    1970 Volume 20 Issue 4 Pages 572-576
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In previous papers, we reported that the activity of drug-metabolizing enzymes was higher in young female rats than in old female rats and that the duration of hexobarbital anesthesia was shorter in the young females than in the old females (1-3). Moreover, it was observed that the induction of microsomal drug-metabolizing enzymes by phenobarbital was more effective in young rats than in old rats (4, 5).
    In the present communication, we wish to report the evidence that, in contrast to the results obtained with rats, clear age difference was not observed in the activity of drug-metabolizing enzymes in mice and there was no clear age difference in the induction of drug-metabolizing enzymes by phenobarbital.
    Download PDF (241K)
  • YOSHIO OHMIYA, HIDEYO OHSHIKA, KENGO NAKAI
    1970 Volume 20 Issue 4 Pages 577-584
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    A number of papers have been presented in support of the concept that epinephrine potentiates barbiturate anesthesia in experimental animals (1-3). Recently, Mazel et al. (4) reported that epinephrine increased the brain level of barbital above controls and suggested that epinephrine may affect the permeability of the blood-brain barrier as well as other barriers. However, mechanism of the potentiating action of epinephrine on barbiturate anesthesia still remained to be elucidated.
    Meanwhile, Ohshika in our laboratory has reported that thiopental bound to plasma albumin can be displaced in vitro by a series of fatty acids (5) and further that anesthetic effect of thiopental was potentiated in rats or mice pretreated with sodium oleate. From a consideration of the results, he suggested the implication of plasma free fatty acids (FFA) in the thiopental anesthesia.
    Several studies (6-8) have demonstrated that the pharmacological effect of a highly bound drug may be increased when the drug is displaced from its binding sites by another drug or substance. Solomon et al. (7) reported that many acidic compounds of unrelated chemical structure bound to a common site on the albumin molecule and that, among them, fatty acids were avidly bound to albumin and acted as effective displacers of another acidic drugs from albumin.
    The well-known relation of epinephrine to FFA in the movement of the latter in and out of adipose tissue (9, 10) and the implication of epinephrine in barbiturate anesthesia suggested a trial of epinephrine under conditions similar those described for fatty acids.
    The purpose of this investigation was to study the potentiating effect of epinephrine, and by comparison, sodium oleate on the thiopental anesthesia. The data presented here indicate that potentiation of thiopental anesthesia may be due to an increased penetration of thiopental into the brain. In addition, observations are also presented indicating that epinephrine may potentiate thiopental anesthesia through its lipolytic action.
    Download PDF (367K)
  • MOTOHIKO UEDA, SABURO MATSUDA, MASARU KAWAKAMI, HIROSHI TAKEDA
    1970 Volume 20 Issue 4 Pages 585-598
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Tanaka et al. (1) have discovered the potent adrenocorticotropic activity of (Gly1)-ACTH (1-18)-octadecapeptide amide (50022), one of the synthetic polypeptide synthesized by Otsuka et al. (2), as well as its lypolytic and MSH activities.
    Since ACTH has several extra-adrenal effects such as induction of stretching and yawning syndrome (3), sexual excitement (4), inhibition of the extinction of conditioned avoidance behaviour (5-7), hypoglycemic effect (8), in addition to its lypolytic and MSH activities, extensive pharmacological studies have been carried out on 50022 (9). The only noteworthy pharmacological effect observed with 50022 was a depressor effect seen in cats and rabbits on intravenous injection.
    This experiment was undertaken to investigate the depressor mechanism of 50022 in experimental animals and to further compare the vascular effect of 50022 with that of vasoactive polypeptides.
    Download PDF (555K)
  • YOSHIHIRO KINOSHITA, HIROYASU KANESHIMA, KENGO NAKAI
    1970 Volume 20 Issue 4 Pages 599-600
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Download PDF (92K)
  • KAZUO WATANABE, YOSHIAKI GOTO, HIDEOMI FUKUDA
    1970 Volume 20 Issue 4 Pages 600-603
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Download PDF (194K)
  • TETSUYUKI NASU, HIDEAKI KARAKI, MIYOSHI IKEDA, NORIMOTO URAKAWA
    1970 Volume 20 Issue 4 Pages 603-605
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Download PDF (157K)
  • K. NAKAMURA, M. GEROLD, H. THOENEN
    1970 Volume 20 Issue 4 Pages 605-607
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Download PDF (158K)
  • SHUJI TAKAORI, CHIKAKO TANAKA
    1970 Volume 20 Issue 4 Pages 607-609
    Published: 1970
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Download PDF (136K)
feedback
Top