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Volume 72, Issue 1-2
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[in Japanese]1976 Volume 72 Issue 1-2 Pages 1-14
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSDownload PDF (684K) -
Masatoshi FUJIMOTO, Toshiharu OHGO, Toshiji IGARASHI, Shinzaburo OHTAK ...1976 Volume 72 Issue 1-2 Pages 15-21
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe present study was performed in order to determine protective effect of dl-α-tocopheryl nicotinate (EN) and dl-α-tocopheryl acetate (EA) on pulmonary edema induced by epinephrine (Epi) in mice. The tocopheryl esters were orally administered once a day for 10 days. Epi was then infused to induce pulmonary edema 3hr after the final dosing. One or three min infusion of 0.01% Epi at a rate of 0.1ml/min provoked toxic syndromes such as piloerection, exophthalmos and salivation. Some animals died of respiratory failure. The lung weight either wet or dry increased after the Epi infusion and diffuse hemorrhage into alveoles was microscopically recognized in untreated animals. However, these findings were of lesser degree in animals receiving NE (20, 50 and 100mg/kg/day) and EA (corresponding doses with EN in molecular weight basis). When comparing the effect of EN with that of EA on the increase of lung weight and death from the Epi infusion, EN was more protective than EA. Although the mechanism of protecting action of these tocopheryl esters remains obscure, the interpretation is that these compounds did not affect the pressor response to Epi.View full abstractDownload PDF (472K) -
(2nd report) Interaction between L-5HTP and p-CPAKenji OHMORI, Tetsuo KOJIMA, Hirohuto MARUMO1976 Volume 72 Issue 1-2 Pages 23-30
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe effect of tryptophan hydroxylase inhibitor p-CPA and 5-HT precursor L-5HTP on conditional avoidance response and 5-HT content in rat brain was examined with the following results: Continuous administration of p-CPA improved the acquisition of conditional avoidance response and retarded the loss of acquired response. Body weight gain was suppressed at the low level. When the conditional avoidance response of the rats reached a certain level, it was suppressed by giving L-5HTP at the doses of 25 and 50mg/kg in the rats given p-CPA, but no effect was observed in the rats given CMC. The 5-HT content in brain was reduced to 22% of control value by a single administration of p-CPA 316mg/kg, but it rapidly recovered to a normal level with L-5HTP administration. From the above results, it was demonstrated that the presence or absence of p-CPA loading causes a significant difference in the appearance of behavior alteration in rats following administration of L-5HTP.View full abstractDownload PDF (482K) -
Kaito TSURUMI, Koichiro GO, Hajime FUJIMURA1976 Volume 72 Issue 1-2 Pages 31-39
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSIn a previous paper, we reported that PZ-177 had potent anti-inflammatory and analgesic activities. In the present work, acute toxicity and action of PZ-177 on the central nervous system were tested in comparison with PZ-222, one of metabolites of PZ-177, and mepirizole. Acute toxicity of PZ-177 was slightly less than that of aminopyrine and the same as that of mepirizole in mice and rats. PZ-177 produced from sedation to loss of righting reflex with the increase of dose. At a low dose with which the righting reflex was hot lost, PZ-177 decreased spontaneous locomotion of mice in the Animex test, produced muscle relaxation in rotarod and inclined screen tests, produced sleeping-pattern in electroencephalogram of rabbit, potentiated hypnosis of barbiturates and exerted an anti-convulsive effect in mice. In these depressive effects on the central nervous system, PZ-222 was very much lower and mepirizole slightly lower than PZ-177. It would thus appear that PZ-177 has more potent analgesic, antipyretic and anti-tussive actions than do PZ-222 and mepirizole.View full abstractDownload PDF (617K) -
Kaito TSURUMI, Akira ABE, Hajime FUJIMURA, Hajime ASAI, Mitsuaki NAGAS ...1976 Volume 72 Issue 1-2 Pages 41-52
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSPZ-177 was found to have potent analgesic, anti-inflammatory and mild central depressive actions. In the present work, the general pharmacological actions of PZ-177 were tested in order to investigate other significant actions and to determine the side effects. PZ-177 showed no significant pharmacological activities on the respiratory and cardiovascular system, on the renal function, on the autonomic nervous system, on the sugar level and coagulation in blood and on local irritation. Volume and acidity of gastric juice were decreased and turn over was not inhibited in the connective tissure. Thus PZ-177 was considered to have no ulcerogenic action on the gastric mucosa. The compound relaxed the tonus of isolated small intestine, tracheal muscles and uterus and stopped spontaneous movement. Moreover the contraction of those smooth muscles by such spasmogens as acetylcholine, histamine serotonin, BaCl2 and oxytocin was inhibited by PZ-177 and the activity was almost the same with each spasmogen. It was found therefore to have spasmolytic activity and no speciflc antagonistic action on the chemical mediators. PZ-177 showed also wear relaxant activity on the skeletal muscle. Those actions on the muscles may have a curative effect on inflammation in bronchotracheal and gastrointestinal tracts or on pain with contraction of skeletal muscle. From the above results, it may be considered that PZ-177 is a relatively safe and useful analgesic and anti-inflammatory compound.View full abstractDownload PDF (2361K) -
Masafumi KOBAYASHI, Takashi YUI, Etsuroh ARAI, Kunio SAWA, Tadashi ASH ...1976 Volume 72 Issue 1-2 Pages 53-58
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe present study was undertaken to determine whether or not adrenalectomy influences anesthesia and increase in brain 5-HT induced by pentobarbital and if such is the case, whether or not aldosterone or ACTH inhibit the effect of adrenalectomy. Male Wistar rats were adrenalectomized or sham-operated and injected with aldosterone (20μg/kg i. p.), ACTH (5.0mg/kg i. p.) or the vehicle (1.0ml/kg i. p.) everyday for 1 week after a postoperative interval of 3 days. These rats ware given a normal diet and 1% saline _??_5% glucose solution. Animals were injected with pentobarbital (50mg/kg i. p.) 18 hr after the last injection of each hormone. It was found that adrenalectomy enhanced “pentobarbital-anesthesia”, although there was no such effect in the adrenalectomized rats pretreated with each hormone. Adrenalectomy inhibited an increase of 5-HT in the brain after pentobarbital, but the hormone pretreatment to those rats did not antagonize the inhibition of the 5-HT increase.View full abstractDownload PDF (394K) -
Atsushi MUKAIDE, Tsutomu KAMEYAMA1976 Volume 72 Issue 1-2 Pages 59-61
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe effects of various drugs on chemotaxis of polymorphonuclear leukocytes (PMN's) in vitro have been studied. Response of rabbit PNM's in vitro to the chemotaxis was found to be suppressed by hydrocortisone succinate, chloroquine hydrochloride, cytochalasin B, colchicine and dibutyl cyclic AMP. On the other hand, 8-bromo-cyclic GMP enhanced the chemotaxis of PMN's.View full abstractDownload PDF (180K) -
Masafumi KOBAYASHI, Shigetoshi FUKUYO, Hajime HIGUCHI, Toshio TAKEUCHI1976 Volume 72 Issue 1-2 Pages 63-70
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSInfluences of hyper- and hypothyroidism on MAOI (tranylcypromine) were studied by measuring the effects on rectal temperature and 5-HT, 5-HIAA and norepiniphrine levels and tyramine uptake in the brain. Hyperthyroidism was accomplished in rats injected with triiodothyronine 0.2mg/kg i. p. every two days for 70 days (long period group) or every day for 5 days (short period group) and hypothyroidism induced by feeding rats a diet to which 0.3% propylthiouracil had been added for 70 days (long period group) or 30 days (short period group). Those controls were treated with a triiiodothyronine vehicle 1.0ml/kg i. p. and fed a normal-balanced diet for each period. All the long period groups were decapitated on the last day and the brains were used for the determination of steady levels of above-cited monoamines. The 5-HT content in hypothyroid rats was considerably higher than euthyroid rats but other determinations in both hyper- and hypothyroid rats did not differ significantly in comparison with euthyroid controls. Each short term group was treated with tranylcypromine 10mg/kg i. p. on the last day. Tranylcypromine brought about a marked hyperthermia in hyperthyroid rats but conversely hypothermia in hypothyroid rats, while “MAOI-induced 5-HT and norepinephrine increase, 5-HIAA decrease and tyramine uptake inhibition in the brain” of hyper- and hypothyroid rats were almost to the same in degree as in euthyroid rats.View full abstractDownload PDF (572K) -
Kenji YAMADA, Yoshio AIZAWA1976 Volume 72 Issue 1-2 Pages 71-75
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSInfluence of denervation on phospholipid metabolism in the vas deferens and effect of phospholipase C treatment on sensitivity of the vas deferens for noradrenaline were studied. The incorporation of 32P-orthophosphate into phosphatidylethanolamine and phosphatidylcholine was markedly increased by denervation. Incorporation of 32P-orthophosphate into proteolipid was accelerated more than that of 3H-leucine. Sensitivity of the denervated vas deferens for noradrenaline was strongly reduced by phospholipase C treatment. These data suggest that the supersensitivity of the denervated vas deferens for noradrenaline was mainly due to the increase in phospholipids.View full abstractDownload PDF (305K) -
Influence of the sex of the animal on antitumor activity of the polysaccharideHitoshi ITO, Sensuke NARUSE, Mamoru SUGIURA1976 Volume 72 Issue 1-2 Pages 77-94
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSWe have already reported antitumor activities of fungal and bacterial polysaccharides on mice. In the present experiment, the influence of the sex on antitumor effects on such material from Grifola umbellata, Coriolus versicolor Fries or Sargassum thunbergii and the immunity of mice against tumor were investigated. The growth velocities of Sarcoma 180, Ehrlich solid carcinoma, Pulmonary tumor 7423 and NF-sarcoma bearing mice both without treatment and those treated with polysaccharides were more rapid in males than in females. The regression rates in mice with the above tumors were higher in females than in males. However, a few DS Mie mice with Sarcoma 180 and A/Jax Mie mice with Ehrlich solid carcinoma regressed spontaneously. The growth velocity of Shionogi carcinoma 42 was not influenced by the sex. On the other hand, both males and females which had experienced a regression of ascites tumor after the administration of polysaccharides rejected the re-implanted Ehrlich ascites carcinoma, Sarcoma 180, NF-sarcoma and Shionogi carcinoma 42. These results suggest that a strong enhancement of immune response occurs in the tumor implanted in the host animal by the administration of polysaccharides. The combination of X-ray irradiation Ehrlich ascites cells and polysaccharides strengthens the antitumor effect of NF-sarcoma and Shionogi carcinoma 42. Peritoneal exudate cells and lymphocytes were compared between the male and female mice after being treated with ATSO and P. GU-1. Such cells were present to a much greater extent in females.View full abstractDownload PDF (1125K) -
Hiroyoshi SHINO1976 Volume 72 Issue 1-2 Pages 95-104
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSAction mechanisms of the contractile agents, K, ACh and Ba and of the antispasmodics, Cd and Mn were investigated. The contractions by K, ACh and Ba are exponential in shape, but consisted of phasic contraction (PC) and the subsequent tonic contraction (TC). PC by K and ACh are initiated by the release and the passive influx of Ca, whereas the PC by Ba is due to the release of Ca. On the other hand, TC by these three agents is maintained by the active influx of Ca requiring energy. Since only the contraction by Ba remains constant in Ca (-) bath solution, it is assumed that the direct stimulation to muscle contractile elements without the mediation of Ca mobilization is also partly related to the contracting mechanism of Ba. Storage sites of Ca in the cell membrane of this preparation are distinguished into three divisions, the first, the second and the third, which contains loosely-, less loosely-, and tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh does so from the first and the second divisions, and Ba does so from all of the three divisions. The following assumption was obtained on the antispasmodic action of Cd and Mn, on the basis of the influence of Ca removal from bath solution and of addition of high K to bath solution and the analysis with concentration-action curves. The antispasmodic mechanism of Cd and Mn is due to inhibition of cell membrane (competitive inhibition of influx and then release of Ca and subsequently competitive and non-competitive inhibition of influx and release of Ca) followed by the non-competitive inhibition of muscle contractile system, with the increase of dosage.View full abstractDownload PDF (527K) -
Kohtaro TANIYAMA, Hiromasa ARAKI, Masayoshi MAEDA, Juei-Tang CHENG, Hi ...1976 Volume 72 Issue 1-2 Pages 105-111
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe contractile mechanisms of K, ACh and Ba were investigated in relation to the mobilization of Ca in the rat's isolated rectum. Contractions by K, ACh and Ba consisted of the phasic contraction and the subsequent tonic contraction. From the effects of metabolic inhibition (anoxia, DNP) and Ca removal from bath solution on the contractions by these three agents, the following assumptions have been made: the phasic contractions by K and ACh are induced by the release of Ca from the store sites and the passive influx of Ca, whereas that by Ba is induced by the release of Ca. The tonic contractions by K and ACh are maintained mainly by the active influx of Ca, whereas that by Ba is maintained by the active influx of Ca and the release of Ca. In addition, the direct stimulation to the contractile elements of muscle is partly concerned with the Ba-induced contraction. In the muscle cell membrane, three divisions of Ca stores; the first is the store where Ca is most easily released, the second is the store where Ca is comparatively easily released and the third is the store where Ca is not easily released. K releases Ca from the first store, ACh does so from the first and second stores, and Ba does so from these three stores for producing contraction. These assumptions were further supported by the analysis of the concentration-action curves of the influence of Ca removal from bath solution on the phasic contractions and the tonic contractions induced by the three agents.View full abstractDownload PDF (457K) -
Shigeru IKEDA, Satoshi MURAYAMA1976 Volume 72 Issue 1-2 Pages 113-126
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSNeuropharmacological studies were undertaken to investigate the mode of action of perimetazine. 1) Sedation, hypothermia, muscle relaxation and other signs of central depressant effects were observed after perimetazine administration in the rabbit. 2) Neuro-muscular transmission was not affected by intravenous injection of perimetazine, but was slightly facilitated by a large dose of intraarterial injection of the drug. 3) Perimetazine slightly depressed spinal reflex potentials in the spinal cat and markedly reduced them in the anaesthetized cat and the decerebrate cat. 4) Perimetazine reduced decerebrate rigidity in the rabbit, and decreased muscle spindle discharges in the decerebrate cat. 5) Perimetazine had no effect on the response of superior cervical ganglion but suppressed the response of the cat nictitating membrane. 6) In the rabbit, perimetazine elicited a drowsy pattern in the spontaneous EEG and inhibited the EEG arousal response induced by auditory stimulation, but failed to depress the EEG arousal response induced by electric stimulation of the mesencephalic reticular formation. These results suggest that perimetazine has central nervous system depressant effects such as sedative and muscle relaxant effects, and its mode of action is similar to that of chlorpromazine.View full abstractDownload PDF (3311K) -
Reiko UEBA1976 Volume 72 Issue 1-2 Pages 127-137
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe mechanism of catecholamine (CA) release induced by transmural stimulation (TS) and the participation of acetylcholine (ACh) in this mechanism were studied using isotonic contraction of excised vas deferens of rats. Furthermore, the inhibitory effect of bretylium (Br) on sympathetic activity was observed. Results: 1) The effects of various kinds of drugs on isotonic contractions induced by TS, exogenous ACh and exogenous noradrenaline (NA) were observed with the results shown in Table 1. The following has been concluded: (1) TS-induced contraction is due to stimulation of the endings of hypogastric nerve (sympathetic nerve), resulting in CA release from adrenergic fiber (AF) and ACh release from cholinergic fiber (CF) in this nerve. (2) The participation of ACh is not indispensable in the CA release from AF induced by TS. (3) Endogenous ACh release from CF by TS brings about CA release under eserine application. (4) CA release by exogenous ACh is not inhibited by ganglion blockade, but is inhibited by atropine, indicating the muscarinic receptor to be in AF endings. 2) Br exerted preferentially the irreversible inhibition on CA release from AF rather than that on ACh release from CF, while it caused a mild reversible inhibition on CA release by exogenous ACh. 3) On the TS contraction that had been abolished irreversibly by Br, NA incubation showed a mild lasting recovery, while methamphetamine (MAP) or calcium (Ca) incubation showed a strong lasting recovery. Furthermore, in this recovery of TS contraction, the incubation with NA or MAP exerted only the recovery of CA release, while the Ca incubation exerted the recovery of both CA release and ACh release. It would appear that Br blocks both AF and CF by inhibiting the transmitters-releasing action of Ca.View full abstractDownload PDF (722K) -
Yasuhiko FURUTA, Machiko WASHIZAKI1976 Volume 72 Issue 1-2 Pages 139-144
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe cardiovascular effects of fusaric acid, a dopamine-β-hydroxylase (DBH) inhibitor and a hypotensive agent, and 5-(4'-chlorobutyl) picolinic acid, one of the most potent DBH inhibitors in fusaric acid derivatives, were investigated in anesthetized dogs. Fusaric acid (10-30 mg/kg) given intravenously caused immediately and dose-dependently a fall in blood pressure, an increase in heart rate, a stimulation of respiration, a marked increase in the rate of superior mesenteric arterial flow, and a decrease in the rate of femoral arterial flow. Fusaric acid (0.3-3 mg) given close-arterially caused a dose-dependent decrease in the sinus rate and in the developed tension in isolated blood-perfused sinoatrial node and papillary muscle preparations, respectively. For the superior mesenteric, renal, and femoral circulations which were perfused with blood, a close-arterial injection of fusaric acid (10-30 mg) increased in the rates of flow in a dose-dependent manner. 5-(4'-Chlorobutyl) picolinic acid showed similar responses as fusaric acid quantitatively or qualitatively. These results indicate that hypotension induced rapidly after intravenous administration of fusaric acid or 5-(4'-chlorobutyl) picolinic acid is not due to the enzyme inhibition, but rather to the direct depression of cardiac function and decrease in peripheral vascular resistance.View full abstractDownload PDF (394K) -
Fundamental studies on assuming drug toxicity. In vitro lvsis of lysosomes and erythrocytes by drugsTaro OGISO, Mihoko WATANABE, Keiko YAMAUCHI, Tamiko SATO, Yoshio KATO1976 Volume 72 Issue 1-2 Pages 145-151
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSThe effect of drugs on isolated rat liver lysosomes, erythrocytes and some erythrocyte enzymes was studied in vitro. Many tranquilizers, antihistaminics and antidepressants, which are known to have the greatest number of adverse reactions in clinical use, had a lytic effect on the particle membranes at concentrations above 2×10-4M. The present study revealed a good correlation between the p. o. LD50 (rat and mouse) and H30 (molar concentration of drug causing 30% hemolysis.) It is suggested, therefore, that the labilizing effect of drugs on rat erythrocytes is useful for testing the lytic action of drugs in vivo.View full abstractDownload PDF (437K) -
Shigenori WATANABE, Hiromu KAWASAKI, Showa UEKI1976 Volume 72 Issue 1-2 Pages 153-168
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSElectroencephalographic (EEG) effects of lopramine, a new antidepressant, were investigated in rabbits with chronic electrode implants, and compared with those of imipramine and amitriptyline. All drugs were administered i. v. Lopramine (10, 20mg/kg) induced a drowsy pattern of spontaneous EEG consisted of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal thetha waves. Imipramine and amitriptyline (1-5mg/kg) also elicited similar EEG changes but were much more potent than lopramine in this effect. Lopramine (10, 20mg/kg) failed to suppress the EEG arousal responses induced by not only auditory stimulation but also electrical stimulation of the mesencephalic reticular formation, centromedian thalamus and posterior hypothalamus, whereas imipramine and amitriptyline (1_??_5 mg/kg) markedly inhibited these responses. The EEG arousal response induced by i. v. injection of physostigmine 0.1mg/kg showed no change after lopramine (20mg/kg), while the response was significantly suppressed by imiprarnine (2, 5mg/kg) and amitriptyline (1, 2mg/kg). Lopramine showed no effect on the recruiting response induced by electrical stimulation (8Hz) of the centromedian thalamus and slightly enhanced the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while imiprarnine (2, 5mg/kg) and amitriptyline (1-5mg/kg) caused an initial depression followed by sustained enhancement of these afterdischarges. These results demonstrate lopramine to be an antidepressant of a new type which has no effect on the ascending reticular activating system and no central anticholinergic action.View full abstractDownload PDF (1286K) -
Masayoshi MAEDA1976 Volume 72 Issue 1-2 Pages 169-176
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSAntispasmodic mechanisms of isoproterenol and papaverine were investigated in relation to the mobilization of Ca in the rat's isolated rectal muscle. The findings on the relaxing effects of isoproterenol and papaverine on the contractions induced by increasing concentrations of K and on the modifications in the shape of K- and ACh-induced contractions by these two agents suggest that the antispasmodic mechanism of isoproterenol may be related to inhibition of the transmembrane influx of Ca as well as release of Ca. whereas that of papaverine may be related to not only inhibition of the transmembrane influx of Ca and release of Ca but also to inhibition of the ability of contractile elements responding to Ca. Furthermore, analysis of the concentration-action curves of K and acetylcholine concerning the phasic and the tonic contractions affected by isoproterenol and papaverine (Table 1) provide additional evidence for such a hypothesis.View full abstractDownload PDF (464K) -
Masayoshi MAEDA1976 Volume 72 Issue 1-2 Pages 177-184
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSInfluence of the Na removal from bath solution on the antispasmodic actions of isoproterenol and papaverive against the phasic contractions by K and acetylcholine were investigated in relation to the mobilization of Ca in isolated rectal strip from the rat. Effect of the Na removal on the uptake of intracellular Ca into storage sites was also examined. The Na removal attenuated the inhibitory actions of isoproterenol and papaverine on the release of Ca, whereas the Na removal did not affect the inhibitory action of isoproterenol on Ca influx and that of papaverine on the response of the muscle contractile elements. Furthermore, the Na removal inhibited the uptake of intracellular Ca into storage sites. Thus, it is suggested that isoproterenol and papaverine may generate the inhibitory action on the release of Ca by accelerating Ca uptake into storage sites, therefore the antispasmodic actions of these agents are depressed by the deprivation of Na from the bath solution which attenuates the Ca uptake.View full abstractDownload PDF (550K) -
Hideo MIZUSAWA, Mikio YAMANE, Ken SAKAI1976 Volume 72 Issue 1-2 Pages 185-199
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSEffects of ifenprodil tartrate, a potent vasodilator, on the autonomic, peripheral and central nerve system were studied in experimental animals. In isolated vas deferens of guinea pigs, the contraction in response to noradrenaline and sympathetic nerve stimulation was competetively antagonized by ifenprodil 10-7-10-5M (pA2: 7.69 against noradrenaline). Ifenprodil (50_??_1, 000μg/kg i. v.) inhibited the contraction of cat nictitating membrane and dog urinary bladder induced by sympathetic nerve stimulation. Ifenprodil (250_??_1, 000μg/kg i. v.) lowered adrenaline-induced lethality (ED50: 360μg/kg). The drug produced a hypermotility of guinea pig uterus, and showed a transient hypertonus of dog gut which was abolished by atropine. Ifenprodil (10_??_20mg/kg i. v.) inhibited the propulsion of charcoal meal in mice. In Shay rats, more than 10mg/kg i. m. of the drug inhibited the secretion of acid gastric juice and the ulceration. Ifenprodil showed a potent local anesthetic action in the guinea pig cornea and skin. The spontaneous EEG of rabbits showed a resting pattern (0.25_??_2mg/kg i. v.) followed by an arousal pattern (5_??_10mg/kg). Ifenprodil (20_??_100mg/kg p. o.) potentiated a hypnosis induced by barbital, and potentiated pentylenetetrazol, strychnine and picrotoxin induced convulsion. The drug (20 and 100mg/kg p. o.) lowered the body temperature of rats. From these results it is concluded that ifenprodil produces a blocking action of α-adrenoceptors in various smooth muscle preparations and a direct relaxation of the smooth muscle itself without affecting the motor and central nerve systems.View full abstractDownload PDF (1652K) -
Ippei OHMURA1976 Volume 72 Issue 1-2 Pages 201-210
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSShapes of the contractions induced by K, acetylcholine (ACh), histamine and Ba consisted of the phasic contraction (PC) and the subsequent tonic contraction (TC). PCs by K, ACh and histamine are initiated by the release and the passive influx of Ca, whereas that by Ba is only initiated by the release of Ca. TCs by K, ACh and histamine are maintained by the active influx of Ca, whereas that by Ba is maintained by the active influx and the release of Ca. Storage sites of Ca in the cell membrane of this preparation can be divided into three; the first, the second and the third, which contain the loosely, the less loosely-, and the tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh or histamine does so from the first and second divisions, and Ba does so from all of the three divisions. Based on the influence of high Kdepolarizing bath solution on the relaxations by isoproterenol (Iso) and papaverine (Pap) and the effects of Iso and Pap on the shapes of contractions by K, ACh, Ba and exogenous Ca, the following assumptions were made: antispasmodic action of Iso is produced by inhibition of cell membrane (inhibition of release and influx of Ca), whereas that by Pap is due to this inhibition followed by inhibition of the muscle contractile system with the increase of concentrations. The effects of Iso and Pap on the concentration-action curves of the contractions by K, ACh, Ba and exogenous Ca (Table II) suggest that the parallel shift to the right of the curves of K, ACh and Ba is due to the functional antagonism between the antispasmodics and the mobilization of Ca produced by the contracting agents.View full abstractDownload PDF (682K) -
Junichi KITAGAWA, Katsuya IWATSUBO, Yoshio SHIGENAGA, Reizo INOKI1976 Volume 72 Issue 1-2 Pages 211-227
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSGeneral pharmacological properties of enflurane (E) and halothane (H) were investigated. Maximum bloodconcentrations of both drugs reached 30min after inhalation. E showed lower maximum blood concentration, initial velocity of uptake and shorter half life than H. Neither drug had any effect on neuromuscular junction, but E increased N-M effect of succinylcholine. Both drugs decreased tension of uterine and intestine muscles. Poly- and monosynaptic reflexes were inhibited more by H. ED50's of E and H for righting reflex were 1.25 and 1.40%, respectively. Tonic and clonic convulsions and death induced by electric shock were inhibited more by E. Almost equal anticonvulsive potency was observed for chemoshocks. Death due to electric and chemoshock was remarkably inhibited by both drugs. Spontaneous EEG was altered in a different manner, although flattened with spikes at 4% concentration of both drugs. E altered rhythmicity of recruiting response and both drugs inhibited this response. H inhibited more remarkably the augmenting response and E inhibited the arousal response. E increased negative potentials of the primary response evoked by sensory stimulation, while H decreased these potentials. Both drugs completely inhibited the secondary response.View full abstractDownload PDF (2922K) -
Yoshimichi MURAYAMA, Satoru WATANABE, Yasuko HAYASHI1976 Volume 72 Issue 1-2 Pages 229-236
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSResults of a previous experiment indicated that osmotic pressure and sodium concentration in distal tubular fluid of the nephron constantly microperfused were increased during natriuresis of fasting rats. The present experiments were performed in order to clarify whether or not water reabsorption and urea movement in Henle's loop, which may modify osmotic pressure and sodium concentration in distal fluid, change in the fasting rat kidney. Non-fasting, 18_??_24 hours and 4_??_5 days-fasting rats were used. After surgical procedures, the animal was infused with 2% saline at 33.3μl/min. The loop of Henle was perfused with 1% saline containing 0.05% lissamine green, 3H-inulin and 14C-urea at 29.1nl/min. In the fasting groups, urinary flow and sodium excretion were increased, whereas urea excretion was depressed and inulin clearance showed a tendency to decrease. Tubular fluid to plasma ratio of osmotic pressure in the distal tubule was elevated without change of water reabsorption. From present and previous results, the increases of osmotic pressure and sodium concentration in distal tubular fluid of fasted rat kidney cannot be explained from an increase of water reabsorption in the Henle's loop. Consequently, natriuresis with fasting may contribute partially to an inhibition of sodium reabsorption in Henle's loops, possibly in the thick ascending limbs. Recovery of C-urea perfused into Henle's loops of fasted rats increased.View full abstractDownload PDF (603K) -
Analytical method of conflict-induced behavior in rabbitsSaizo YANAURA, Kousei MINEO, Youichi ABE1976 Volume 72 Issue 1-2 Pages 237-248
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSAn at tempt was made to induce conflict behavior in rabbits by conditioning under hypothalamic electrical stimulation. Behavioral analysis was performed using our newly devised technique which employs the use of a vibration apparatus fixed to head and waist, and a recording of various behavior. Conditioning was carried out by sensory stimuli flight behavior. Reinforcement was as follows : the CS used was flickering light photic (10Hz, 10μsec., ) and acoustic (250Hz, 15 dB) and UCS electrical stimulation (100Hz, 1 msec, , not exceeding 2v) in the medial hypothalamic area and peri-fornix. The restrained animals were placed on a table in an acoustically isolated room with a discrete monotonous back ground noise. CRs were obtained within a short time as were responses: (1) During the autonomicsomatic responses, (2) continuous run and (3) non-continuous run. Data obtained during the non-continuous run represent a conflict-induced type of behavior which may be applied in studies related to the psychopharmacological actions of drugs.View full abstractDownload PDF (790K) -
Ippei OHMURA1976 Volume 72 Issue 1-2 Pages 249-258
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSDibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction (PC) and tonic contraction (TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine. induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentrationaction curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site.View full abstractDownload PDF (619K) -
Effects of methylcobalamin and cobamide on EMG patterns and weight-loss of denervated muscles following crush of the sciatic nerve in ratsKiyomi YAMATSU, Takeru KANEKO, Akifumi KITAHARA, Isao OHKAWA1976 Volume 72 Issue 1-2 Pages 259-268
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSExperiments were performed to investigate the effects of Vitamin B12, i.e., methylcobalamin and cobamide, on the neural degeneration and regeneration. Male Wistar rats (140 to 150g) under conditions of experimental unilateral sciatic nerve crushing were treated consecutively with methylcobalamin (50 and 500μg/kg/day i. p.), cobamide (50 and 500μg/kg/day i. p.) or saline. EMG recordings were periodically carried out and rats of each group were sacrificed to determine the weight-loss of denervated muscles 1, 2, 3 and 4 weeks after crush. Neither methylcobalamin nor cobamide exerted any significant effect on body-weight gain of the nerve-crushed rats with a daily injection of 50 and 500μg/kg i. p.. The EMG pattern of the denervated biceps femoris muscle showed a total lack of fibrillation for 2 days after the nerve-crush. Thereafter, the fibrillation appeared and continued for 10 to 14 days until the nerve had regenerated, as evidenced by the appearance of a complex NMU voltage. The occurrence of fibrillation voltage was slightly delayed in methylcobalamin group (500μg/kg/day) as compared with the saline control group. The re-appearance of normal NMU voltage was more rapid in the methylcobalamin 500μg/kg group than in controls and other experimental groups. Neither methylcobalamin nor cobamide had any significant effect on the weight-loss of the gastrocnernius and tibialis anterior muscles following crush of the sciatic nerve. However, a daily injection of 500μg/kg of methylcobalamin produced a significant increase in the weight of the soleus muscle which recovered to the extent of being the same weight of the contralateral 4 weeks after the nerve-crush. These results suggest that methylcobalamin may have an inhibitory effect on Wallerian degeneration and also a facilitatory effect on the neural regeneration of the crushed sciatic nerve of rats.View full abstractDownload PDF (698K) -
Effects of methylcobalamin on mitosis of Schwann cells and incorporation of radio-active leucine into protein fraction of crushed sciatic nerve in ratsKiyomi YAMATSU, Yoshiharu YAMANISHI, Takeru KANEKO, Isao OHKAWA1976 Volume 72 Issue 1-2 Pages 269-278
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSMale Wistar rats (140 to 150g) in which the unilateral sciatic nerve had been crushed were treated consecutively with methylcobalamin (5, 50 and 500 μg/kg/day i. p.) or saline immediately after the nerve-crush. Thereafter, they were periodically sacrificed for biochemical and histological examinations. At different intervals after the nerve-crush, L-leucine-4, 5-T (20μCi/100g, specific activity 15mCi/m mole) or L-leucine-14C (U) (15μCi/100g, specific activity 270mCi/m mole) was given i. p. to some rats of each group and 3hr later they were sacrificed to determine the rate of leucine incorporation into protein fractions of the crushed nerve and the denervated muscles. The nerve and muscles of the contralateral side served as control. Longitudinal sections of proximal and distal stumps of the sciatic nerve were prepared and stained with hematoxylin and eosin. As compared with saline group, repeated injections of 5, 50 and 500μg/kg/day of methylcobalamin caused a significant increase of the in vivo incorporation of radioactive leucine into the proteinfraction of the crushed sciatic nerve 5 to 7 days after the crush. In contrast, a recovery of the increased incorporation of leucine into the crushed nerve was more rapid in methylcobalamin groups than in the saline group.On the other hand, methylcobalamin (5_??_500μg/kg/day i. p.) had no significant effect on the leucine incorporation into the denervated muscles (m. gastrocnemius, m. tibialis anterior and m. soleus). In addition, consecutive injections of methylcobalarnin (5_??_500μg/kg/day) did not affect the mitosis of Schwann cells during the period of Wallerian degeneration of the crushed sciatic nerve. These results suggest that methylcobalamin possesses a stimulating effect on proteosynthesis in Schwann cells at the initial stage of axon regeneration and it may facilitate neural regeneration.View full abstractDownload PDF (730K) -
[in Japanese], [in Japanese]1976 Volume 72 Issue 1-2 Pages 279-286
Published: 1976
Released on J-STAGE: July 30, 2010
JOURNAL FREE ACCESSDownload PDF (637K)
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