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Volume 46 (1988)
- Issue 4 Pages 319-
- Issue 3 Pages 205-
- Issue 2 Pages 101-
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Volume 46, Issue 4
Displaying 1-16 of 16 articles from this issue
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Masahiro ITONAGA, Tsutomu URUNO, Kazuhiko KUBOTA1988 Volume 46 Issue 4 Pages 319-324
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTwo β-carboline esters, methyl or ethyl β-carboline-3-carboxylate, β-CCM and β-CCE, were found to antagonize the antinociceptive and satiety action of the sulfated octapeptide cholecystokinin (CCK8) which was administered intracisternallyto mice. β-CCM did not affectthe antinociception induced by morphine. The two β-carboline esters weakly inhibited the food intake in mice. However, when they were administered after CCK8 administration, they reversed the CCK8-induced satiety. Since the two β-carboline esters have been previously shown to act as selective cholecystokinin (CCK) receptor antagonists in the isolated guinea-pig gallbladder muscle, they are suggested to antagonize the central action of CCK through acting on the CCK receptor in the central nervous system. The results obtained from the present paper also suggest that benzodiazepine receptor ligands seem in general to act as CCK receptor antagonists as well.View full abstractDownload PDF (327K) -
Hideaki KARAKI, Minori MITSUI1988 Volume 46 Issue 4 Pages 325-330
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSEffect of verapamil, a Ca2+ channel blocker, on the contractions in the intestinal smooth muscle of taenia isolated from guinea-pig caecum was examined. In normal medium, 10 mM-80 mM KCl or 10-7 M-10-5 M carbachol induced a transient contraction followed by a sustained one. When the muscle strips were treated with a Ca2+-free solution for 2 min, these stimulants failed to induce contraction except an initial transient contraction induced by 10-6M-10-5M carbachol. Cumulative application of verapamil during the sustained contraction induced muscle relaxation. Higher concentration of verapamil was needed to inhibit the sustained contraction induced by 10 mM or 20 mM K+ than that induced by 40 mM or 80 mM K+. Similarly, the sensitivity to verapamil of the sustained contraction induced by 10-7 M carbachol was lower than that induced by 10-6 M or 10-5 M carbachol. In the presence of verapamil, addition of either high K+ or carbachol induced an initial transient contraction, although the sustained contraction was strongly inhibited. These results suggest that high K+ and carbachol activate two types of Ca2+ channels; lower concentrations of the stimulants open the channel which is less sensitive to verapamil, and higher concentrations open the channel which is more sensitive to verapamil.View full abstractDownload PDF (321K) -
Hisashi MATSUDA, Johji YAMAHARA, Goro KOBAYASHI, Hajime FUJIMURA, Kazu ...1988 Volume 46 Issue 4 Pages 331-335
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSEffects of alismol, a sesquiterpenoid isolated from the rhyzome of Alisma orientale, on adrenergic mechanisms were examined in the isolated rabbit ear artery. Alismol (10-6 to 10-4- M) inhibited the contraction of isolated rabbit ear artery by electrical stimulation of the perivascular nerves. The inhibition was concentrationdependent; at a concentration of 10-4 M, the inhibition was 90% (n=8). Treatment with 10-4 M alismol inhibited the increase in 3H-noradrenaline (3H-NAd) release induced by electrical stimulation by 63±6%. Alismol at 10-4 M did not affect the neuronal uptake of 3H-NAd in the artery. Alismol at 10-4 M slightly inhibited contractions induced by exogenously administered NAd. These results demonstrate that alismol inhibits the adrenergic neuro-effector mechanisms in rabbit ear artery, and they suggest that alismol acts primarily on nerve terminals and inhibits their responses to electrical stimulation by interfering with NAd release.View full abstractDownload PDF (244K) -
Jun HIROI, Kaname OHARA, Katsumasa KOBAYASHI, Takashi FUJITSU, Takashi ...1988 Volume 46 Issue 4 Pages 337-348
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe antiallergic activity of sodium 10-(2, 3-dimethyl pentanamido)-4-oxo-4H-pyrimido [1, 2-C] quinazoline-3-carboxylate•hydrate(FR50948) was studied and compared with the activities of sodium cromoglycate (SCG) and lodoxamide. FR50948 had inhibitory effects on type I and type III allergic reactions, but not on type II and IV allergic reactions. FR50948 also had weak inhibitory effects on inflammation (carrageenin paw edema and adjuvant arthritis) and SRS release from rat neutrophils, but no antagonistic effects to histamine and serotonin. The inhibitory effect of FR50948 on IgE-mediated type I allergic reactions was essentially the same as those of SCG and lodoxamide, because FR50948 inhibited the histamine release from rat peritoneal mast cells and had cross tachyphylaxis with SCG in the rat PCA test. However, FR50948, like lodoxamide, had a stronger activity than SCG and was effective by the oral route, unlike SCG which was effective only by the parenteral route. Furthemore, the inhibitory effects of FR50948 on type III reactions and inflammatory reactions were much more potent than those of SCG and equal to those of lodoxamide, and the effect on IgG-mediated PCA was stronger than that of either reference drug. These results suggest that FR50948 will be beneficial in clinical use.View full abstractDownload PDF (584K) -
Harumi MITSUHASHI, Keitaro HASHIMOTO1988 Volume 46 Issue 4 Pages 349-358
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSAntiarrhythmic effects of AHR 10718 were examined using two-stage coronary ligation, digitalis and adrenaline-induced canine ventricular arrhythmias and aconitine-induced canine atrial arrhythmia. The minimum effective plasma concentration for each arrhythmia model was determined for quantitative analysis of the antiarrhythmic effects. AHR 10718 suppressed the above arrhythmias except for adrenaline-induced arrhythmia. The minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation and digitalis were 8.1±0.7 (by 10 mg/kg, i.v.), 2.9±0.9 (by 5 mg/kg, i.v.) and 2.8±0.6 (by 5 mg/kg, i.v.) μg/ml, respectively (mean±S.D., n=6). The correlation coefficients between the antiarrhythmic effects of AHR 10718 and its plasma concentrations were not high. This pharmacological profile is characteristic of class 1 Na channel blockers, and in particular, it is similar to those of disopyramide, procainamide and SUN 1165 from our previous studies. AHR 10718 is expected to become a clinically useful antiarrhythmic drug.View full abstractDownload PDF (531K) -
Yoshihiro KADOWAKI, Tetsuro OHTA, Nobuo HOTOKEBUCHI, Sadatoshi KIMOTO, ...1988 Volume 46 Issue 4 Pages 359-372
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSWe examined effects of 711389-S, a new antiarrhythmic agent, on ouabain-induced arrhythmias in dogs and guinea-pigs, aconitine-induced arrhythmias in dogs and mice, adrenaline-induced arrhythmias in dogs under an anesthetized condition, and arrhythmias induced by coronary artery ligation and occlusion by a glass bead in dogs under conscious and un-restrained conditions. 711389-S (1-3 mg/kg, i.v.) decreased the number of ventricular extrasystoles induced by ouabain in dogs, and the doses of ouabain required to induce various types of arrhythmias were increased by pretreatment of guinea-pigs with intraduodenal application of 711389-S (5-10 mg/kg). In mice, 711389-S (3 mg/kg, i.v. or 10 mg/kg, p.o.) significantly prolonged the time to onset of arrhythmias induced by aconitine infusion. Atrial fibrillation induced by a topical application of aconitine on the atrium was blocked by 711389-S (1 mg/kg, i.v.) in dogs. 711389-S (1-3 mg/kg, i.v.) depressed arrhythmias induced by adrenaline and restored the sinus rhythm by significantly decreasing the number of ventricular ectopic beats induced by coronary ligation or occlusion in dogs. Oral administration of 711389-S (10-30 mg/kg) in dogs markedly depressed the ventricular ectopic beats induced by coronary ligation. The half decay time of 711389-S after a single bolus injection of 711389-S ranged from 60 to 80 min. Results indicate that 711389-S has similar antiarrhythmic effects to those of other Class I antiarrhythmic agents in situ, and they suggest that this compound might have potential usefulness as a new type of antiarrhythmic agent for clinical use.View full abstractDownload PDF (742K) -
Kenzo TAKAGI, Takaaki HASEGAWA, Takafumi KUZUYA, Kenji OGAWA, Takako W ...1988 Volume 46 Issue 4 Pages 373-378
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSStructure-activity studies were carried out to compare the relaxant effects of various xanthine derivatives synthesized by substitution of the alkyl groups of the N3 position in the xanthine molecule. We evaluated the relaxant effects and the inhibitory activities on c-AMP phosphodiesterase (PDE) in tracheal smooth muscle isolated from guinea pigs. A comparative study on their pharmacokinetic characteristics was also carried out in rabbits. Dose-dependent relaxant effects were observed, and the relaxant effect of propylxanthine was nearly equal to the effects of butyl- and isobutylxanthines. Based on the estimation of the Ki values for PDE inhibition, it was found that butylxanthine is a potent inhibitor of PDE. There was good correlation between the alkyl chain length and the Ki value of these derivatives. The results showed that the alkyl chain length plays an important role in the inhibition of PDE. There were no significant differences in the volume of distribution, although the half-life showed significant differences. It is likely that the half-lives of these derivatives are affected by their chain lengths. The present study indicated that butylxanthine may be a new candidate as a bronchodilator. However, clinical studies have to be carried out to compare its efficacy and adverse effects with those of existing bronchodilators such as theophylline.View full abstractDownload PDF (312K) -
Yoshiyuki MIYAMOTO, Masanobu OZAKI, Hiroyuki YAMAMOTO1988 Volume 46 Issue 4 Pages 379-386
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effects of adrenalectomy on the pharmacokinetics and antinociceptive activity of morphine were investigated to elucidate the mechanism of adrenalectomy-induced potentiation of morphine antinociception in rats. Plasma concentrations of morphine were estimated specifically and serially in each rat by high performance liquid chromatography with an electrochemical detector. After the intravenous administration of 10 mg/kg morphine, the plasma half-life of morphine was significantly prolonged by adrenalectomy without any effect on the volume of morphine distribution. After the subcutaneous administration of 7 mg/kg morphine, pharmacokinetic parameters were changed by adrenalectomy in the same manner as after intravenous administration. In contrast, after the subcutaneous injection of 3.5 mg/kg morphine, adrenalectomy failed to change the pharmacokinetic parameters. The antinociceptive potency of subcutaneously administered morphine was enhanced by adrenalectomy for both doses of morphine (3.5 and 7 mg/kg). Morphine antinociception at the dose of 3.5 mg/kg, s.c., in the adrenalectomized group was equipotent with that of 7 mg/kg, s.c., in the sham-operated group, but plasma morphine concentrations for 3.5 mg/kg, s.c., in the adrenalectomized group were significantly lower than those for 7 mg/kg morphine, s.c., in the sham-operated group. These results suggest that the enhancement of morphine antinociception by adrenelectomy can not be explained by the increased morphine level alone.View full abstractDownload PDF (501K) -
Hidehiko NABATAME, Masashi SASA, Shuji TAKAORI, Masakuni KAMEYAMA1988 Volume 46 Issue 4 Pages 387-395
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSMicroiontophoretic studies using rats anesthetized with chloral hydrate were performed to elucidate the relationship between the striatal cholinergic system and nigrostriatal dopaminergic system. lontophoretic application of carbachol inhibited the spikes elicited by substantia nigra (SN) stimulation in 21 of 24 caudate neurons in which the spikes induced by SN stimulation were inhibited by microiontophoretically applied domperidone, a dopamine D-2 receptor antagonist. This inhibitory effect was completely blocked by atropine, although the spike generation induced by SN stimulation remained unaffected by the drug. However, carbachol did not affect the glutamate-induced firing of the caudate neurons of which the spikes induced by SN stimulation were inhibited by application of both domperidone and carbachol. Furthermore, carbachol had inhibitory effects on the spikes induced by SN stimulation even after the systemic application of bicuculline. In contrast, in 17 of 24 caudate neurons in which the spikes induced by SN stimulation were not affected by domperidone, carbachol did not inhibit the spikes induced by SN stimulation. These results suggest that the muscarinic receptors located on the SN-derived dopaminergic nerve terminals mainly play a role in inhibiting inputs from the SN to the caudate neurons, probably by reducing the release of dopamine from the nerve terminals.View full abstractDownload PDF (615K) -
Tadashi NAGAMATSU, Yoshio SUZUKI1988 Volume 46 Issue 4 Pages 397-402
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSIn the present study, we investigated whether prostaglandin E1 (PGE1) could accelerate the disposal of heat-aggregated BSA (a-BSA) in the glomerulus by mesangial cells and/or resident mesangial cells. ICR mice were injected i.v. with 90 mg/100 g B.W. of a-BSA 3 times at 4-hr intervals. Kidneys were isolated at various times after the first injection of a-BSA. The location of a-BSA in the glomerulus was then detected by immunohistochemical staining and immunofluorescence. A-BSA was detected in the mesangium and along capillary walls by both techniques. The amount of glomerular a-BSA increased with time, attaining a peak about 12 to 14 hr after the first administration of a-BSA and then disappeared by 36 hr after. The mice injected with a-BSA 3 times received 150, 200, 300 and 400 μg/mouse of PGE1, s.c., and 200 and 400 μg/mouse of PGE2 or PGF2α, s.c., at 12 hr; and their kidneys were isolated at 16 hr. The mice with 300 and 400 μg/mouse of PGE1 had 34.3% and 37.6% less a-BSA than the control mice, respectively. Additionally, the mice with 400 μg/mouse of PGE2 had 63.2% less a-BSA than the control mice. However, PGF2α failed to reduce glomerular a-BSA to a level less than that of the control. In conclusion, we confirmed that PGE1 accelerates breakup of macromolecules by mesangial cells and/or resident mesangial cells in the glomerulus.View full abstractDownload PDF (452K) -
Tsutomu SUZUKI, Yoko KOIKE, Yasuhiro CHIDA, Miwa MISAWA1988 Volume 46 Issue 4 Pages 403-410
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSWe investigated the characteristics of physical dependence on methaqualone. Rats were made physically dependent on methaqualone by the use of the drug-admixed food (DAF) method for 33 days. Pentobarbital, barbital, ethanol and diazepam were cross-administered against methaqualone to evaluate the degree of suppression of methaqualone withdrawal signs as an index for the cross-physical dependence liability of these drugs to methaqualone. To evaluate the cross-physical dependence liability, we used AUC of body weight loss and withdrawal scores between the first cross-administration (9 hr after the withdrawal) and 27 hr after the withdrawal. AUC of weight loss was significantly suppressed by the four test drugs as compared to each control. Withdrawal scores were also significantly inhibited by the cross-administration of barbital, ethanol and diazepam. Considering that the rats given barbital or ethanol fell asleep after the cross-administration, diazepam seems to cause the strongest suppression of methaqualone withdrawal signs among the four test drugs. Thus, physical dependence on methaqualone may be similar by nature to that on benzodiazepines rather than barbiturates and alcohol.View full abstractDownload PDF (422K) -
Hitoshi KONTANI1988 Volume 46 Issue 4 Pages 411-413
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSTwo or five-Hz electrical stimulation of the central end of the left pelvic nerve severed from the urinary bladder in rats inhibited bladder contraction induced by intravesical infusion of Tyrode's solution. Inhibition of bladder motility by 2-Hz nerve stimulation appeared after pretreatment with strychnine (0.3 mg/kg, i.v.), naloxone (1 mg/kg, i.v.) and picrotoxin (1 mg/kg, i.v.). Hypogastric nerve stimulation, however, did not affect bladder contraction. These results suggest the presence of an inhibitory mechanism on the pelvic motoneuron activated by contralateral pelvic nerve stimulation in rats.View full abstractDownload PDF (155K) -
Tetsuhiro HISAYAMA, Naomi KUMAGAI, Issei TAKAYANAGI1988 Volume 46 Issue 4 Pages 414-417
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThirty-min treatment of guinea-pig taenia caecum with 300 nM propylbenzilylcholine mustard (PrBCM) shifted the concentration-response curve for carbachol to the right with a reduction of the maximum contraction, but 90-min treatment did not result in further inhibition. Under these conditions, pilocarpine hardly contracted the preparations, and it competitively antagonized carbachol. Muscarinic agonists might interact with two types of receptor mechanisms and carbachol elicited a stimulus from both types, whereas pilocarpine did so predominantly from the PrBCM-sensitive one.View full abstractDownload PDF (187K) -
Masakatsu TAKAHASHI, Shogo TOKUYAMA, Hiroshi KANETO1988 Volume 46 Issue 4 Pages 418-420
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSDiazepam, an antianxietic agent, antagonized the stress-induced analgesia (SIA) distinctively depending on the characteristics of the stress. Psychological (PSY, using communication box)-SIA was completely blocked by 1 or 2 mg/kg of diazepam in the tail pinch (TP) method, but not antagonized by 1 mg/kg of the drug in the tail flick test. Swimming-SIA was resistant to diazepam in both methods, and footshock-SIA was only suppressed slightly by 2 mg/kg in the TP method. Thus, emotional factors play an essential role in the production of PSY-SIA, although the participation of the factors in the other SlAs can not be excluded.View full abstractDownload PDF (183K) -
Yukio FUJINO, Koji NAKAYAMA, Kuniyoshi YOSHIMURA, Yutaka FURUYA, Takar ...1988 Volume 46 Issue 4 Pages 421-423
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSA diet containing cholesterol and cholic acid (SID) is known to induce the formation of cholesterol fatty liver as well as cholesterol gallstones. The activity of HMG-CoA reductase, one of the key enzymes for cholesterol synthesis in the liver, is significantly lowered by addition of β-muricholic acid to SID. The prevention of fatty liver formation by β-muricholic acid was accompanied by the suppression of HMG-CoA reductase activity.View full abstractDownload PDF (174K) -
Koichi YOSHIOKA1988 Volume 46 Issue 4 Pages 424-427
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSPharmacological responsiveness of isolated strips of the canine hepatic veins was investigated. Circular strips showed a low responsiveness to 5-hydroxytryptamine, a low sensitivity to norepinephrine and a high sensitivity to histamine. Longitudinal strips developed greater tensions to norepinephrine than circular strips. An excitatory cholinergic component was demonstrated in contractile responses of longitudinal strips to transmural stimulation. Acetylcholine-induced contraction was potentiated by physostigmine. These results indicate that the hepatic veins belong to the group of “veins of the digestive tube”.View full abstractDownload PDF (193K)
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