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Volume 48 (1988)
- Issue 4 Pages 395-
- Issue 3 Pages 307-
- Issue 2 Pages 157-
- Issue 1 Pages 1-
Volume 48, Issue 2
Displaying 1-20 of 20 articles from this issue
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Kayo AKIYAMA, Den'etsu SUTO1988 Volume 48 Issue 2 Pages 157-164
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effect of W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide), a calmodulin antagonist, on the calcium-bound conformation of calmodulin was studied by 1H-NMR at 400 MHz. W-7 affected the resonances of Ile-27, Phe-68, Phe-92, Ile-100, His-107 and Val-142. The resonances of Met-71, Met-72, Met-76, Phe-89 and Phe-141 may be affected by W-7. These find ings suggest that W-7 binds to hydrophobic amino acid residues, which almost occur in calcium-binding sites II, III and IV or their vicinity. The effect of W-7 on the structure of calmodulin was similar to that of other drugs, trifluoperazine, D600 and oxmetidine. Thus, those residues in the high-field methyl region, the methionine methyl region and the phenylalanine aromatic region of calmodulin, which were similarly affected by all four drugs, may be important at the interface for binding of calmodulin to the regulatory sites on target enzymes.View full abstractDownload PDF (641K) -
Taeko HATA, Tomitaro KITA, Eiji ITOH, Ritsuko OYAMA, Atsufumi KAWABATA1988 Volume 48 Issue 2 Pages 165-173
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSNeurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, has been observed clinically to be effective for treating pain in patients with lumbago, SMON and other neuropathies. In the present study, we examined the mechanism of the antinociceptive effect of neurotropin in mice in relation to administration routes, opioids, and noradrenergic or GABAergic drugs, by the tail pressure method. The antinociceptive effects of neurotropin were large when administered by the i.p. and intracisternal (i.cist.) routes, but comparatively small in the case of the intrathecal (i.th.) route. Neurotropin may thus act at the supraspinal level rather than on the spinal cord. The antinociceptive effect of neurotropin was not blocked by naloxone, and no cross-tolerance developed between neurotropin and morphine. The effect of neurotropin was blocked by phentolamine and reserpine, but not by atropine. Its effect was enhanced by GABA, muscimol, aminooxyacetic acid and diaminobutyric acid, but not by baclofen, and blocked by bicuculline methiodide. From these results, the antinociceptive action of neurotropin appears to be non-opioid in nature, and may possible be mediated by the noradrenergic and GABAergic systems, but unrelated to the cholinergic system.View full abstractDownload PDF (643K) -
Yoshiki IWABUCHI, Chihiro AOKI, Taizo MASUHARA1988 Volume 48 Issue 2 Pages 175-184
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe actions of four choline esters, acetylcholine (ACH), methacholine (MET), carbachol (CAR) and bethanechol (BET), on the secretion of saliva and the specific glycoprotein (GP) contained in the secretory cells of the submandibular gland (SMG) of the rat were compared under conditions with and without physostigmine (PHY). The ED50 values with respect to salivation were 17 mg/kg for ACH, 1060 μg/kg for BET, 810 μg/kg for MET and 75 μg/kg for CAR, whereas after pretreatment with PHY, ED50 values were lowered to 7.5 mg/kg for ACH and 212 μg/kg for MET, but remained unchanged for CAR and BET. SDS-polyacrylamide gel electrophoresis demonstrated that the saliva from the SMG elicited by the four choline esters contained GP I (130 KDa) and GP IV (21.5 KDa), characteristic of the acinus, and a band of GP III (31 KDa), which originates from the granular tubules. The order of intensity of these bands was band I>>band III=band IV. Among these bands, band I increased in intensity in a dose-dependent manner. These results suggest that the four choline esters act mainly on the acinar cells, but exert some effects on the granular tubules of the rat SMG.View full abstractDownload PDF (709K) -
Akira SHIMADA, Toshiharu TSUDA, Tomoji YANAGITA1988 Volume 48 Issue 2 Pages 185-193
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe mechanism of antinociceptive interactions among morphine, cocaine and alcohol was studied in mice, guinea pigs and rabbits. In the tail-pressure test in mice, cocaine and alcohol alone showed almost no antinociceptive effects at doses up to 8 mg/kg, s.c., and 4 g/kg, i.g., respectively. Alcohol at 2 g/kg, i.g., also did not influence the effect of morphine, while cocaine at 4 mg/kg, s.c., significantly potentiated the antinociceptive effects of not only morphine but also pentazocine. In an analysis of serum and brain concentration levels of morphine in mice, when morphine and cocaine were simultaneously administered at 2 mg/kg, s.c., and 4 mg/kg, s.c., respectively, both serum and brain levels of morphine showed neither increase nor decrease in comparison with the levels in mice administered morphine alone. In myenteric plexus-longitudinal muscle preparations of isolated guinea pig ileum, 1 μM cocaine enhanced the agonistic effects of both pentazocine and ethylketocyclazocine. Furthermore, cocaine as well as ethylketocyclazocine showed naloxone-reversible agonistic effects in isolated rabbit vas deferens. These results indicate that cocaine may potentiate the antinociceptive effects of morphine and pentazocine by acting on the κ-opioid receptors as an agonist.View full abstractDownload PDF (727K) -
Hisashi KURIBARA, Sakutaro TADOKORO1988 Volume 48 Issue 2 Pages 195-201
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSEffects of tertiary anticholinergic drugs, atropine (1.3, 2.5, 5 and 10 mg/kg, s.c.) and scopolamine (0.13, 0.25, 0.5 and 1 mg/kg, s.c.), and a quarternary anticholinergic drug, methylatropine (1.3, 2.5, 5 and 10 mg/kg, s.c.), on the drinking behavior were investigated in water non-deprived rats that were housed in a 12-hr light-dark situation (light period: 6:00-18:00) with a free access to food. Atropine, 5 mg/kg, and scopolamine, 0.13 and 0.25 mg/kg, administered at 12:00, significantly increased the drinking during the 12:00-18:00 period. Furthermore, lower to medium doses of atropine increased the drinking during the 18:00-6:00 period. In contrast, the drinking did not change during the 12:00-18:00 period, but decreased during the 18:00-6:00 period in a dose-dependent manner after administration of methylatropine at 12:00, whereas the drinking during the 18:00-24:00 period decreased in a dose-dependent manner when both the tertiary and quarternary drugs were administered at 18:00. However, the drinking during the 24:00-6:00 period increased in the rats that were administered atropine at the dose of 5 or 10 mg/kg at 18:00, while the drinking still decreased after methylatropine at the same time. The present results suggest that in water non-deprived rats, central muscarinic cholinergic blockade is effective for both increasing and decreasing drinking behavior, depending on the doses, when the drug is administered, and time span between the drug administration and the behavior observation. It is also suggested that peripheral cholinergic blockade monotonously suppresses the drinking behavior.View full abstractDownload PDF (491K) -
Michio YAMAMURA, Hiroyuki NAKAGAWA, Kiyoshi KINOSHITA, Takashi OCHIAI, ...1988 Volume 48 Issue 2 Pages 203-212
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSBehavioral pharmacological studies on mafoprazine, a new drug for the prevention of aggressive behavior, were performed to compare its effects with those of an existing drug, azaperone (Stresnil®). The acute toxicity of mafoprazine in mice was slightly stronger than that of azaperone. Mafoprazine showed the following effects (at 0.2 to 2.0 mg/kg, s.c.): a decrease in spontaneous motor activity, prolongation of the duration of pentobarbital anesthesia, inhibition of longterm isolation-induced aggressive behavior, inhibition of olfactory bulbectomy-induced hyperemotionality and muricide behavior in mice and rats, and a marked taming and tranquilizing effect on aggressive behavior in dogs. These effects of mafoprazine were qualitatively the same as those of azaperone. Mafoprazine showed cataleptogenicity in rats at 5 mg/kg, s.c. or more and motor incoordination in rats at 0.2 mg/kg, s.c. or more. In the experiment on operant behavior in rats, the effect of mafoprazine on differential reinforcement of the low rate (DRL) response was almost the same as those of azaperone and chlorpromazine. These results indicate that mafoprazine has substantially the same psychotropic effect as azaperone, while the former has a weaker action on the extrapyramidal system than the latter, suggesting that mafoprazine could be used as a unique aggression-inhibiting drug.View full abstractDownload PDF (804K) -
Katsuya HIGO, Hiroshi SAITO, Norio MATSUKI1988 Volume 48 Issue 2 Pages 213-221
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe binding properties of a 1, 4-dihydropyridine (DHP) calcium entry blocker, [3H]nimodipine, to a microsomal fraction from rat vas deferens was characterized. The specific binding was saturable, rapid and reversible. Scatchard analysis of the binding revealed a single binding site, and the dissociation constant and the maximum number of binding sites were 0.31±0.02 nM and 97.0±7.19 fmol/mg protein, respectively. Both the Kd value obtained from the kinetic study and the IC50 value from relaxation of the K+-depolarized organ were approximately 0.4 nM, indicating that the binding site is closely related to the functional Ca2+ channel. The specific [3H]nimodipine binding was displaced by DHP derivatives at low concentration and by verapamil at high concentration, but diltiazem had no effect on the binding. Calcium chelating agents decreased the [3H]nimodipine binding which was restored by adding Ca2+. 5'-Guanylylimidod1phosphate caused a rightward shift of the displacement curve for Bay K 8644 but not for nimodipine, suggesting the involvement of guanine nucleotide binding protein in the signal transduction between the DHP binding site and the Ca2+ channel.View full abstractDownload PDF (754K) -
Mitsuru KAKIHANA, Masahiro SUNO, Akinobu NAGAOKA1988 Volume 48 Issue 2 Pages 223-228
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe hypotensive action of CV-4093·2HCl (CV-4093), a new calcium antagonist, was studied in spontaneously hypertensive, renal hypertensive, DOCA-salt hypertensive and normotensive rats. CV-4093 (3 and 10 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in the three types of hypertensive rats. At the dose of 10 mg/kg, the compound decreased the blood pressure to the normotensive level between 1 and 3 hr after it was administered; the antihypertensive effect lasted for at least 8 hr. The systolic blood pressure in normotensive rats was also decreased at 3 and 10 mg/kg, p.o., but less evidently than in the hypertensive rats. When the antihypertensive effect of CV-4093 was compared with that of seven known calcium antagonists in spontaneously hypertensive rats, it was the most potent and the most long-lasting.View full abstractDownload PDF (355K) -
Junichiro AONO, Kazushige SAKAI1988 Volume 48 Issue 2 Pages 229-239
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSExperiments in vitro and in vivo were undertaken to examine possible involvement of a central effect in the hypotensive mechanism of SGB-1534. SGB-1534 selectively antagonized the contraction of isolated rat aortae to phenylephrine with a pA2 value of 10.57, 3.9 times higher than prazosin, and markedly displaced the α1-adrenoceptor ligand 3H-prazosin (pK1: 8.81) in rat brain. In anesthetized spontaneously hypertensive rats (SHRs), SGB-1534 (0.3-3 μg/kg) and prazosin (3-30 μg/kg) given intravenously (i.v.) and intracerebroventricularly (i.c.v.) produced a dose-dependent and long-lasting depressor response associated with no change in heart rate (HR). The two drugs (i.c.v.), however, significantly attenuated the pressor response to i.v. noradrenaline. Single i.v. injections of SGB-1534, prazosin and yohimbine dose-dependently inhibited the St 587 (a highly specific and centrally acting α1-adrenoceptor agonist) enhanced flexor reflex and the pressor response to i.v. phenylephrine in pithed rats. However, the activities of SGB-1534 and prazosin in inhibiting the St 587-enhanced flexor reflex were 16, 000 and 660 times, respectively, less than those in attenuating the pressor response to i.v. phenylephrine. It seems that the hypotensive action of SGB-1534 is due to the peripheral α1-adrenoceptor antagonistic mechanism rather than the central one.View full abstractDownload PDF (855K) -
Takahiro IWAMOTO, Tominori MORITA, Toshiro KANAZAWA, Hiroshi OHTAKA, K ...1988 Volume 48 Issue 2 Pages 241-247
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effect of KB-2796, a new diphenylpiperazine calcium antagonist, on [3H]nitrendipine ([3H]NTD) binding was investigated in synaptosomal membranes prepared from the guinea pig cerebral cortex. KB-2796 inhibited [3H] NTD binding in a dose-dependent manner with an IC50 value of 86 nM. In this respect, KB-2796 was the most potent among the diphenylpiperazine derivatives tested. Saturation binding data indicated that this inhibition resulted from a decrease in the binding affinity without changes in the maximal number of binding sites. KB-2796, however, significantly increased the dissociation rate constant of [3H] NTD from radiolabeled membranes. This finding suggests that KB-2796 inhibits [3H]-NTD binding by a negative heterotropic allosteric mechanism. Other diphenyl-piperazines tested also showed similar inhibitory properties. Diphenylpiperazines may act at a site, which is different from the 1, 4-dihydropyridine binding site, on the voltage-dependent calcium channel.View full abstractDownload PDF (467K) -
Takumi SATOH, Hideaki KARAKI1988 Volume 48 Issue 2 Pages 249-255
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSContractile effects of ouabain and K+-free solution on rat aortic strips were investigated. In the aorta without endothelium, application of ouabain or K+-free solution produced, after a latency period, a slow contraction reaching the maximum after 80-100 min. Pretreatment of the muscle with either indomethacin (20 μM) or verapamil (1 μM) decreased the maximum level of these contractions, whereas verapamil, but not indomethacin, prolonged the latency period. Simultaneous application of these inhibitors showed additive inhibitory effects. In the presence of endothelium, the latency period slightly increased without changing the maximum contractile tension. Methylene blue (5 μM) shortened the latency period only in the aorta with endothelium. These results suggest that the contractions of rat aorta induced by ouabain and K+-free solution are due not only to membrane depolarization and Na+-Ca2+ exchange but also to the release of prostaglandins. Endothelium-derived relaxing factor seems to inhibit a part of these contractions.View full abstractDownload PDF (505K) -
Ikuko KIMURA, Leonora-Rivera PANCHO, Takayuki SHIOIRI, Masayasu KIMURA1988 Volume 48 Issue 2 Pages 257-262
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe suppression of spontaneous Ca2+ spikes and isometric contractions by gingerols and their chemically related compounds was examined using the single sucrose gap method. Most of the congeners tested suppressed spontaneous contraction, which was not necessarily accompanied by the suppression of Ca2+ spikes. The most potent analogues for Ca2+ spike suppression were (±)-[6]-gingerol (0.3 mM) and (±)-yakuchinone-A (0.3 mM). These compounds also strongly inhibited spontaneous contraction. In contrast, (±)-[8]-gingerol (0.3 mM) inhibited the contraction without changing the Ca2+ spikes. These results suggest that the inhibition of spontaneous contraction induced by (±)-[6]-gingerol, but not by (±)-[8]-gingerol, is due to the Ca2+ spike suppression.View full abstractDownload PDF (367K) -
Yutaka MATSUOKA, Masafumi SAKUMA, Toshihiko SUGIOKA, Yasufumi TERAWAKI ...1988 Volume 48 Issue 2 Pages 263-272
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSCharacteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, β-phenylethylamine (PEA) and β-hydroxyphenylethylamine (OHPEA), were examined. The pain threshold of mice was measured by using the hot plate method. Intraperitoneal administration of α-methyl-p-tyrosine inhibited antinociception induced by PEA and OHPEA, and intracisternal administration of norepinephrine increased antinociception induced by PEA and OHPEA. Intracisternal administration of phentolamine inhibited the antinociception induced by PEA derivatives. The levels of norepinephrine and normetanephrine in the brain were determined by using H PLC. PEA derivatives decreased norepinephrine in the brain and tended to increase normetanephrine at 15 min after the administration of PEA derivatives. These findings indicate that PEA derivatives cause the release of norepinephrine in the central nervous system, and the released norepinephrine induces antinociception.View full abstractDownload PDF (668K) -
Keitaro HASHIMOTO, Kozo WATANABE, Atsushi SUGIYAMA1988 Volume 48 Issue 2 Pages 273-282
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSUsing two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of pirmenol were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. Pirmenol suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation, digitalis and adrenaline were 1.1±0.3 (by 3 mg/kg, i.v.), 1.1±0.3 (by 3 mg/kg, i.v.), 1.1±0.2 (by 3 mg/kg, i.v.) and 2.5±1.5 (by 3 mg/kg, i.v.) μg/ml, respectively (mean±S.D.M., n=6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine, tocainide and cibenzoline. Since pirmenol had no deleterious effects on the blood pressure and sinus node activity, its clinical usefulness is expected.View full abstractDownload PDF (625K) -
Masaaki ISHIKAWA, Giichi TAKAYANAGI, Ken-ichi SASAKI1988 Volume 48 Issue 2 Pages 283-286
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe effect of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the selenium induced-lethality was examined in mice. A single injection of BSO (500 mg/kg, i.p.) markedly decreased the concentration of GSH in the liver after 5 hr. The acute lethality induced by selenium was greatly increased in BSO-treated mice. In contrast, the selenium induced-lethality decreased by pre- and post-treatments of cysteine (100 mg/kg, i.p.) in mice.View full abstractDownload PDF (231K) -
Susumu SATOH, Toshiyuki MATSUOKA, Mizue SUZUKI-KUSABA, Kiyoshi CHIBA1988 Volume 48 Issue 2 Pages 287-289
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSIn pentobarbital-anesthetized dogs, the increase in the renal norepinephrine secretion rate elicited by renal nerve stimulation (1 Hz) during infusion of angiotensin I (15 ng/kg/min) was partially but significantly inhibited (by 21-37%) after dosing with cilazaprilat (0.1 mg/kg), an angiotensin converting enzyme inhibitor, accompanied by a decrease in the renal venous plasma norepinephrine concentration. These results may suggest that cilazaprilat exerts at least a part of its hypotensive effect through decreasing the facilitatory action of endogenous angiotensin II on adrenergic transmission.View full abstractDownload PDF (263K) -
Masayasu KIMURA, Masashi MUROI, Ikuko KIMURA, Shin-ichiro SAKAI, Isao ...1988 Volume 48 Issue 2 Pages 290-293
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe neuromuscular blocking actions of several constituents extracted from Japanese-sino medicine, aconite, were compared in mouse phrenic nerve-diaphragm muscle preparations. Hypaconitine (HAT) was more potent than aconitine (ATN), mesaconitine (MAT) and deoxyaconitine. Lipohypaconitine, coryneine and lipodeoxyaconitine were less effective. Lipoaconitine, benzoyl-mesaconine, higenamine, kobusine and chasmanine were not effective. The blockades by HAT, ATN and MAT were not recovered by neostigmine. The mechanisms of blockade were similar to that of aconite crude extract. These results suggest that aconite action is dependent on HAT, a main constituent.View full abstractDownload PDF (290K) -
Takashi KONDOH, Ikuko KIMURA, Masayasu KIMURA1988 Volume 48 Issue 2 Pages 294-298
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSThe 86Rb efflux by high K+ was measured simultaneously during the mechanical responses in pig duodenal circular muscle using a superfusion technique. A slightly higher K+ (17.7-23.6 mM) simultaneously induced tetrodotoxin (TTX)-sensitive relaxation and 86Rb efflux. Much higher K+ (47.2-143.4 mM) contracted and also increased the 86Rb efflux markedly, but the extent of TTX-sensitive efflux remained the same as the one at 17.7-23.6 mM K+, indicating that the TTX-insensitive efflux was contraction-related. The former efflux may lead to hyperpolarization linked to relaxation.View full abstractDownload PDF (314K) -
Kunihiko YOKOTANI, Yasunobu OKUMA, Yoshitsugu OSUMI1988 Volume 48 Issue 2 Pages 299-302
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSEffects of DQ-2511, a new peripherally acting anti-ulcer agent, on vagally induced gastric acid output and mucosal blood flow (MBF) were investigated in urethane-anesthetized rats with gastric fistula. Intravenous infusion of DQ-2511 (2 or 20 mg/kg/hr, for 30 min) reduced the vagally induced gastric acid output and MBF, and these inhibitory effects were abolished by pretreatment with phentolamine. The DQ-2511-induced inhibition of acid output was abolished with yohimbine, but not with prazosin. These observations suggest that DQ-2511 possesses the properties of an adrenergic alpha-2-adrenoceptor agonist. DQ-2511 presumably acts on adrenergic alpha-2-adrenoceptors located on the parasympathetic neurons in the gastric wall, thereby reducing the vagally-induced gastric acid output.View full abstractDownload PDF (283K) -
Norio MATSUKI, Shinya UENO, Takahide KAJI, Akane ISHIHARA, Chao-Hsiung ...1988 Volume 48 Issue 2 Pages 303-306
Published: 1988
Released on J-STAGE: August 25, 2006
JOURNAL FREE ACCESSAcute emetic responses to seven cancer chemotherapeutic agents (adriamycin, bleomycin, cisplatin, cyclophosphamide, 5-fluorouracil, methotrexate, mitomycin C) were studied in the Suncus murinus. Intravenous injection of the drugs caused vomiting with various latency. Cisplatin-induced emesis was prevented by the pretreatment with metoclopramide or chlorpromazine but not with domperidone. These results indicate that the Suncus murinus is a useful animal for testing emetic activities of cancer chemotherapeutics and antiemetic activities of prophylactic drugs.View full abstractDownload PDF (278K)
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