巻号一覧
48 巻 (1988)
- 4 号 p. 395-
- 3 号 p. 307-
- 2 号 p. 157-
- 1 号 p. 1-
48 巻, 3 号
選択された号の論文の12件中1～12を表示しています
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Seiji ICHIDA, Shunji ARIYOSHI, Hiroaki OKA, Tetsuo MURAKAMI, Takashi F ...1988 年 48 巻 3 号 p. 307-316
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーStudies were made on whether the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could he used as a substitute for the contractile response to ACh. This ACh-induced phosphorylase a activity was dependent upon the concentration of ACh and was inhibited by atropine, suggesting that it was linked to muscarinic ACh receptors. Both extracellular calcium and an increase of the intracellular calcium concentration were needed for its activation by ACh. Ca2+-antagonists such as Co2+, diltiazem, nitrendipine and verapamil inhibited the ACh-induced activity, suggesting that the activation by ACh required the influx of calcium ions into the uterine muscle through Ca2+-antagonist sensitive Ca2+ channels. The IC50 values of CoCl2, diltiazem, nitrendipine and verapamil on the ACh-induced phosphorylase a activity were 3.4 × 10-3M, 2.5 × 10-4M, 2.5 × 10-5M and 1.1 × 10-4 M, respectively. These values were comparable with the IC50 values of these Ca2+-antagonists on the contractile response of isolated rat uterine muscle segments to 3 × 10-4 M ACh. The inhibitory effects of Co2+, nitrendipine and verapamil, but not diltiazem, on ACh-induced phosphorylase a activity were attenuated by higher concentrations of CaCl2 (0.36 to 2 mM). These findings suggested that the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could be used as a substitute for the contractile response to ACh.抄録全体を表示PDF形式でダウンロード (472K) -
Akira FUJII, Noboru KUBOYAMA, Sumi KOBAYASHI, Yoshikazu NAMIKI, Toyoyu ...1988 年 48 巻 3 号 p. 317-322
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーTime-course studies on gastric damages in rats caused by nonsteroidal anti-inflammatory drugs (NSAIDs) were performed using a gastroscope, and the readings were quantified to obtain the Congestion-Hemorrhage Index (CHI) for evaluating the potencies of the damaging properties of NSAID. The correlation between CHI and Ulcer Index (UI), the quantified value obtained by the conventional methods, was highly significant at 6 and 24 hr after forced oral administration of NSAID. The peak CHIs of aspirin (300 mg/kg), indomethacin (60 mg/kg), mefenamic acid (300 mg/kg) and fenoprofen calcium (300 mg/kg) appeared approximately 24 hr after a single forced oral administration of drugs. Thus, it was suggested that an observation at 24 hr in addition to one at 6 to 7 hr might be necessary for the examination of damaged gastric mucosa. Under the present experimental conditions, fenoprofen calcium caused the greatest damages on gastric mucosa among the four NSAIDs. Mefenamic acid showed the least damaging potency on gastric mucosa, having a smaller CHI than that of aspirin. Indomethacin possessed a stronger damaging property than aspirin.抄録全体を表示PDF形式でダウンロード (376K) -
Yoshiyuki INADA, Masao TANABE, Katsumi ITOH, Hirosada SUGIHARA, Kohei ...1988 年 48 巻 3 号 p. 323-330
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーCV-5975, (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine-5-acetic acid, was found to inhibit rabbit lung angiotensin converting enzyme (ACE) activity with an IC50 of 3.1 × 10-9 M and a K1 of 2.6 × 10-9 M, inhibit the angiotensin I (A-I)-induced contraction of the guinea pig ileum with an IC50 of 1.3 × 10-8 M, and augment the bradykinin (BK)-induced contraction of the ileum with an AC50 of 9.2 × 10-10 M. The activity of CV-5975 was comparable to or slightly more potent than that of enalaprilat. The overall inhibition constant (Ki*), calculated from a steady-state analysis of enzyme reactions, was 4.4 × 10-12 M for CV-5975; this indicates that the inhibition was about 5 times more potent than that of enalaprilat (2.0 × 10-11 M). In rats, CV-5975 (0.03 and 0.3 mg/kg, i.v. and 3 and 10 mg/kg, p.o.) inhibited the A-I-induced pressor action more potently and for a longer period than did the corresponding doses of enalaprilat and enalapril. CV-5975 and enalapril (3 mg/kg, p.o.) augmented the BK-induced depressor action to a similar extent. In dogs, CV-5975 (0.3 and 1 mg/kg, p.o.) markedly inhibited the A-I-induced pressor action in a dose related manner, and the duration of this inhibitory activity was longer than with the corresponding doses of enalapril. These data provide evidence for the proposal that CV-5975 is a highly potent and long lasting ACE inhibitor.抄録全体を表示PDF形式でダウンロード (601K) -
Naoki NISHINO, Hiroshi FUJIWARA, Sadako A. NOGUCHI-KUNO, Chikako TANAK ...1988 年 48 巻 3 号 p. 331-339
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe activity of glutamic acid decarboxylase (GAD) and choline acetyl-transferase (ChAT) as presynaptic markers of γ-aminobutyric acid (GABA)- and acetylcholine (ACh)-containing neurons, and the binding of [3H]muscimol and [3H]quinuclidinyl benzilate ([3H]QNB) as postsynaptic ones were measured in autopsied samples of the caudate nucleus, putamen, pallidum, substantia nigra and the cerebral cortex from L-dopa-treated patients with Stage V (terminally bedridden) patients with Parkinson's Disease (PD). In PD, GAD activities were significantly reduced in the caudate nucleus and substantia nigra relative to normal controls, but were normal when the values from protracted terminal illness (PTI) cases were used as the controls. ChAT activities were reduced in all regions studied. These reductions in GAD and ChAT activities were not accompanied by a concomitant increase in the density of GABAA or muscarinic receptors. GABAA receptor densities were significantly decreased in both the cortical and subcortical brain regions, while muscarinic receptor densities remained unchanged. We suggest that the decreased density of GABAA receptor in PD brains reflects degeneration of neurons on which the receptor is localized, i.e., degeneration of ascending mono-aminergic neurons including nigral dopamine (DA) neurons.抄録全体を表示PDF形式でダウンロード (759K) -
Apichartpichean RUTTIKORN, Kenzo TAKAGI, Masayuki NADAI, Takafumi KUZU ...1988 年 48 巻 3 号 p. 341-347
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーA new xanthine derivative bronchodilator, 1-methyl-3-propylxanthine (MPX), and 1-methyl-3-butylxanthine (MBX) were synthesized. We evaluated their relaxant effects on tracheal smooth muscle isolated from guinea pigs and pharmacokinetic characteristics in rats using 1, 3-dimethylxanthine (theophylline, TPH) as the reference drug. Dose-dependent relaxant effects were observed in the concentration range of 1 × 10-6 to 1 × 10-4 M, and both MPX and MBX exert very much stronger relaxant effects than TPH with nearly equal potency. There were significant differences in the pharmacokinetic and physico-chemical properties among these drugs, both MPX and MBX having shorter half-lives, higher plasma protein binding in vivo and stronger hydrophobicity compared to TPH. The present study suggested that the N3-alkyl chain length is significant for increasing the relaxant effect and affecting the pharmacokinetic and physico-chemical properties of these drugs.抄録全体を表示PDF形式でダウンロード (481K) -
Kiyoshi OIZUMI, Hiroyuki KOIKE, Toshio SADA, Masaaki MIYAMOTO, Hiroshi ...1988 年 48 巻 3 号 p. 349-356
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーCS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.抄録全体を表示PDF形式でダウンロード (610K) -
Tatsuo MIZOKAWA, Kiyo KIMURA, Yukihiro IKOMA, Kimio HARA, Nozomu OSHIN ...1988 年 48 巻 3 号 p. 357-364
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーIn order to evaluate the potential usefulness of the drug as an anti-depressant, acute and chronic effects of rolipram, a selective inhibitor of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase were investigated on muricide in olfactory bulbectomized (OB) rats. Upon single administration to OB rats, rolipram at a dosage of 1 mg/kg body weight suppressed the muricide for 2 hr after its administration. As a consequence of daily administration of rolipram, however, the incidence of muricide at 24 hr after the administration was decreased, and more than 60% of the rats did not exhibit the muricide on the 12th day. After the cessation of the administration, the incidence of the muricide returned to the initial level. The suppression of the muricide was not antagonized by several kinds of neurotransmitter blockers. Administrations of phosphodiesterase inhibitors and dibutyryl cyclic AMP as well as desipramine and clomipramine also suppressed the muricide dose-dependently. Repeated administration of desipramine also gave results similar to those of rolipram: repetition of a short suppression on the muricide was followed by the appearance of a long-lasting suppression. Differently from rolipram and desipramine, dibutyryl cyclic AMP did not cause long-lasting suppression, and even the direct effect (75% suppression) observed 30 min after its administration on the first day disappeared during its repeated administration for 14 days. From these results, rolipram was considered to show an antidepressant effect through the inhibition of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase.抄録全体を表示PDF形式でダウンロード (515K) -
Yoshiro KOHJIMOTO, Toshikazu OGAWA, Masahiro MATSUMOTO, Kiyoharu SHIRA ...1988 年 48 巻 3 号 p. 365-371
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe effects of long-term dosing with acetyl-L-carnitine (ALC) were examined in aged rats, and they were compared with those in young rats. ALC significantly reduced the lipofuscin deposition in the brain of aged rats. Emotional parameters such as locomotor activity and rearing behavior are lower in aged rats than in young rats, and these behaviors decreased in both age groups during the experiments. ALC diminished the decrease of these emotional behaviors, especially in rearing behavior in the aged rats. Furthermore, ALC had no effect on body weight gain. These results might reflect one of the main beneficial pharmacological mechanisms of ALC in clinical use.抄録全体を表示PDF形式でダウンロード (1015K) -
Hideo ABE1988 年 48 巻 3 号 p. 373-376
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe present experiments were designed to find a method to facilitate methotrexate (MTX) transfer into rat brain tissue. Adult male Wistar-Kyoto strain rats, anesthetized with pentobarbital-Na, received an infusion of the drug solution to be tested into the right internal carotid artery (5 ml/min, 30 sec) 5 min before injection of MTX (7 mg/kg). After 10 min, the MTX levels in the cerebral hemispheres were estimated as a peak height ratio unit of MTX vs. the internal standard by high performance liquid chromatography. MTX was undetectable in either hemisphere after the pretreatment with saline alone or 15% mannitol-saline. The MTX levels in the right hemisphere were about 10 after the pretreatment with 20% mannitol-saline, while MTX was undetectable in the left hemisphere. In contrast, the MTX levels in the right hemisphere were dose-dependently increased to about 25, 130 and 60, 100, respectively, when nitroglycerin (NTG, 2.5 or 7.5 μg/rat) or nicardipine-HCl (NIC, 1.25 or 2.5 μg, /rat) was administered together with 20% mannitol-saline. These vasodilator drugs, however, had no effect when tested in combination with saline or 15% mannitol-saline. It is assumed that an increase in cerebrovascular blood flow induced by NTG or NIC enhances the MTX transfer into the brain once the blood-brain barrier is opened by hypertonic solutions.抄録全体を表示PDF形式でダウンロード (341K) -
Sinya HASHIMOTO, Hisato SHUNTOH, Kohtaro TANIYAMA, Chikako TANAKA1988 年 48 巻 3 号 p. 377-385
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーThe involvement of protein kinase C in the release of[3H]acetylcholine (ACh) and[3H]norepinephrine (NE) was studied in strips of guinea pig small intestine. 12-O-tetradecanoyl phorbol 13-acetate (TPA), but not 4α-phorbol-12, 13-didecanoate (4α-PDD) potentiated the A23187-evoked release of [3H]ACh and [3H]NE from the strips of small intestine preloaded with [3H]choline and [3H]NE, and the potentiating effect of TPA was inhibited by polymyxin B. High K+-evoked releases of [3H]ACh and [3H]NE in the presence of tetrodotoxin were also potentiated by TPA. These TPA-induced potentiations of the evoked release were greater at a low concentration of external Ca2+ (0.5 mM) than at a high concentration (2 mM). Ouabain induced the release of these neurotransmitters both in the absence and presence of the low concentration of external Ca2+. The ouabain-evoked release was not altered by TPA. These results indicate that the activation of protein kinase C potentiates the vesicular release of ACh and NE at low Ca2+ concentration from the nerve terminals of enteric neurons in the guinea pig small intestine.抄録全体を表示PDF形式でダウンロード (644K) -
Tetsu HAYASHI, Akira KIFUNE, Sakutaro TADOKORO1988 年 48 巻 3 号 p. 387-390
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーMale Wistar strain rats subcutaneously administered haloperidol at the dose of 0.035 mg/kg at 3-4 days interval, 10 times, in the avoidance situation. Enhancement of the prolactin-secreting effect of haloperidol was observed when it was given in the home cages at the 10th day after termination of the repeated administration. In these animals, 3H-spiperone binding sites in the pituitary significantly increased, while the DOPAC/DA ratio in the hypothalamus significantly decreased. The enhancement phenomenon may be produced by a decrease in the activity of dopamine neurons in the hypothalamus.抄録全体を表示PDF形式でダウンロード (290K) -
Emiko FUJII, Teruko NOMOTO1988 年 48 巻 3 号 p. 391-394
発行日: 1988年
公開日: 2006/08/25
ジャーナル フリーAdministration of streptozotocin (STZ, 200 mg/kg, i.p.) to pregnant mice during either the early or middle stages of pregnancy produced diabetic conditions in the mother mice. It reduced the litter size, but did not induce diabetes in the pups. The weights of the liver and kidney per unit body weight of the infants of STZ-treated mother mice were slightly larger, though not significantly, than that of infants from control mothers; however, no increase was observed in the blood glucose or glycosylated hemoglobin (HbA1) values.抄録全体を表示PDF形式でダウンロード (316K)
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