巻号一覧
66 巻 (1994)
- 4 号 p. 397-
- 3 号 p. 281-
- 2 号 p. 167-
- 1 号 p. 1-
66 巻, 4 号
選択された号の論文の14件中1～14を表示しています
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Nobuyuki Kishibayashi, Akio Ishii, Akira Karasawa1994 年 66 巻 4 号 p. 397-403
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーKW-5092 ({1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene} propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory activity and acetylcholine release facilitatory activity. The present study used guinea pig ileal homogenates to examine the inhibitory effects of KW-5092 on the activities of AChE and butyrylcholinesterase (BuChE). KW-5092 inhibited AChE and BuChE with the IC50 values of 6.8 × 10-8 M and 2.4 × 10-5 M, respectively. The IC50 values of neostigmine for AChE and BuChE were 3.6 × 10-8 M and 1.9 × 10-7 M, respectively. HSR-803 (N-[4-[2-(dimethylamino)ethoxy]benzyl]-3, 4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, inhibited AChE and BuChE with the IC50 values of 8.6 × 10-6 M and 6.0 × 10-4 M, respectively. The AChE inhibition by KW-5092 Was reversible and noncompetitive, whereas that by HSR-803 was reversible and uncompetitive. On the other hand, the AChE inhibition by neostigmine was non-competitive when the enzyme was preincubated with this inhibitor for 2 min prior to the addition of the substrate, and it was nearly competitive when the enzyme, the inhibitor and the substrate were incubated simultaneously. The present results demonstrate that KW-5092 is a selective, reversible and noncompetitive inhibitor of AChE with different characteristics from those of neostigmine and HSR-803. The AChE inhibitory action may contribute to its gastroprokinetic effect.抄録全体を表示PDF形式でダウンロード (410K) -
Yasuhiro Tsukimi, Susumu Okabe1994 年 66 巻 4 号 p. 405-412
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWe examined the effect of a liquid diet or a combined diet of liquid plus cellulose on the healing of gastric ulcers induced in rats in comparison with that of solid chow. Ulcers were induced in the fundus of the stomach by luminal application of an acetic acid solution. The healing of ulcers could be divided into two phases based on the healing rate: early phase (days 1 to 10) and late phase (days 10 to 20). The liquid diet, but not the combined one, administered for 10 days significantly accelerated ulcer healing in both the early and late phases. The length of the ruptured muscularis mucosa decreased only in the liquid diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet group was observed only in the late phase, it being markedly inhibited in the liquid diet group. The serum gastrin level significantly decreased in the liquid and combined diet groups in contrast to that in the chow group. The liquid and combined diets significantly reduced gastric mucosal DNA synthesis. We conclude that 1) the healing in this gastric ulcer model comprises two phases, and 2) tissue contraction is a major factor for the healing of gastric ulcers in the early phase, while both tissue contraction and regeneration of the ulcerated mucosa are involved in the healing in the late phase.抄録全体を表示PDF形式でダウンロード (584K) -
Mayumi Mori, Hiromi Tsushima, Toshio Kamiya, Tomohiro Matsuda1994 年 66 巻 4 号 p. 413-419
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーMuscarinic antagonists were injected into the hypothalamic supraoptic nucleus (SON) and their effects on the acetylcholine (ACh) release of this nucleus were studied by in vivo microdialysis techniques. Atropine, AF-DX116 (a M2-receptor antagonist), 4-DAMP (a M3-receptor antagonist) and pirenzepine (a M1-receptor antagonist) concentration-dependently increased the ACh release. The EC50 values for these antagonists were 15 nM for atropine, 7.8 μM for pirenzepine, 0.39 μM for AF-DX116 and 59 nM for 4-DAMP, suggesting the autoregulation of the ACh release through an activation of M2 and M3 subtypes of muscarinic receptors in the SON. The postsynaptic effect of muscarinic receptors on urine outflow was studied by microinjection of selective muscarinic receptor agonists and antagonists into the SON. McN-A-343 (a M1-receptor agonist) had no significant effect on urine outflow. Pre-microinjection of atropine, 4-DAMP, p-F-HHSiD (a M3-receptor Antagonist) or pirenzepine into the SON concentration-dependently attenuated the oxotremorine-induced antidiuresis. In contrast, AF-DX116 and methoctramine had no effect on this oxotremorine-induced action. These results suggest that the M3-subtype may contribute to the antidiuretic actions. Nicotine produced an increase in ACh release in the SON and also induced potent antidiuretic effects, both of which were inhibited by hexamethonium. Thus, in the SON, the ACh release may be autoregulated by M2- and M3-subtypes of muscarinic receptors and the antidiuretic effects of ACh produced through an activation of the M3-subtype.抄録全体を表示PDF形式でダウンロード (495K) -
Mari Okazaki, Ikuko Kimura, Masayasu Kimura1994 年 66 巻 4 号 p. 421-426
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーThe effect of aconitine on acetylcholine (ACh) release from motor nerve terminals in the mouse phrenic nerve-diaphragm muscle preparation was studied by a radioisotope method. Both electrical stimulation-evoked release and spontaneous release of 3H-ACh from the preparation preloaded with 3H-choline were measured. The change in the muscle tension was simultaneously recorded in the same preparation. Aconitine (0.1 μM) increased electrically evoked 3H-ACh release, while at higher concentrations (0.3-3 μM) it decreased the evoked release and muscle tension. High concentrations of aconitine (3-30 μM) caused a concentration-dependent increase in spontaneous 3H-ACh release. All these effects were suppressed by tetrodotoxin. The aconitine-induced spontaneous release consisted of two different components: a Ca2+-dependent phasic release that was inactivated within a few minutes and a Ca2+-independent, long lasting release at a low level. The depression of the Ca2+-dependent quantal release seems attributable to the decline of Ca2+ influx into the nerve rather than inactivation of sodium channels. We conclude that aconitine increases and then decreases electrical stimulation-evoked ACh release from the motor nerve through prolonged activation of sodium channels. Further activation of the channels enhances spontaneous release and the subsequent complete inactivation of the quantal release may be due to block of Ca2+ influx.抄録全体を表示PDF形式でダウンロード (473K) -
Hitoshi Ohmori, Toshitaka Shimada, Masaki Hikida, Toshiyuki Takai1994 年 66 巻 4 号 p. 427-432
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWhen an H-2d-specific cytotoxic T lymphocytes (CTL) clone, FC1, was incubated in the presence of 10-7 M phorbol myristate acetate (PMA) for 10-12 hr, the cytolytic activity of the CTL against H-2d target cells was abrogated, but was reversibly restored to the normal level after subsequent incubation of the cells in PMA-free medium for more than 10 hr. These effects of PMA have been reported (Russell, J.H.: J. Immunol. 133, 907-912 (1984)), but the mode of its action has not been fully investigated. Here, we analyzed the biochemical basis of the PMA-induced loss of cytolytic activity. Cycloheximide completely blocked the restoration of the PMA-suppressed cytolytic activity, suggesting that protein synthesis was required in this process. PMA-treatment did not affect the levels of CD3 and CD8 molecules expressed on the CTL, nor was the level of a CTL-specific serine esterase, BLT esterase, affected by this treatment. However, the target cell-induced release of BLT esterase from the CTL was suppressed if the cells were pretreated with PMA. PMA-treatment of the CTL led to the down-regulation of protein kinase C (PKC) activity by about 50%. On the other hand, staurosporin, an inhibitor of PKC, completely blocked the target cell lysis when added at 10-6 M. These results suggest that the down-regulation of at least some isoform(s) of PKC is responsible for the PMA-induced loss of the cytotolytic activity of CTL.抄録全体を表示PDF形式でダウンロード (402K) -
Keiko Yamamura, Hisashi Iwata, Takashi Osada, Toshihisa Yotsuyanagi, T ...1994 年 66 巻 4 号 p. 433-438
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWe investigated the antitumor effects and tissue distribution of adriamycin (ADR) incorporated into a hydroxyapatite (HAP) bead in a cancer rat model bearing Swarm rat chondrosarcoma. The Porous HAP bead (8.48 mm in diameter, 531±0.7 mg in weight) was used as a model bone graft. One ADR-HAP bead (ADR 0.4mg-6.0mg/bead) was implanted s.c. into a Sprague-Dawley rat at 6 days postinoculation of Swarm rat chondrosarcoma. ADR-HAP beads showed strong antitumor activities in a dose dependent manner. The dose of 6.0 mg/bead showed the highest efficacy with no toxic death: It caused a 98% growth inhibition on Day 31 postinoculation and a survival advantage of a 339% increase in life span. After the implantation of the ADR-HAP bead (0.4 mg/bead/body) and the i.v. administration of an equal dose of free adriamycin, we determined the tissue distribution of ADR for up to 90 days. ADR-HAP bead implanted in the tumors released ADR over a 12-week period in the target area. The diffusion of the drug to other organs such as the heart and liver was very low compared with the tumors. The area under the ADR concentration-time curve (AUC) of the tumors was 181.6 μg·day/g and 5.22 μg·day/g after the implantation of the ADR-HAP bead and the i.v. administration of free ADR, respectively. The targeting index of the tumors, defined as the ratio of the AUC after the implantation of the ADR-HAP bead to that after administration of free ADR, was 34.8. The targeting indices of 0.16 and 0.17 for the heart and liver, respectively, indicate that the implantation of the ADR-HAP bead reduced delivery of ADR to these organs. These results demonstrate that this method of administration may be useful in delivering adjuvant chemotherapy in order to prevent local recurrence in the site of the bony defect after the surgical removal of bone tumors.抄録全体を表示PDF形式でダウンロード (366K) -
Toshio Kumai, Masami Tanaka, Minoru Watanabe, Chie Matsumoto, Shinichi ...1994 年 66 巻 4 号 p. 439-444
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWe investigated the effects of castration and testosterone propionate on sympathetic nervous systems in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Four-week-old male rats were castrated. For replacement of androgen, testosterone propionate (500 μg/rat) was administered subcutaneously 2 times a week to castrated rats after their 14th week. The systolic blood pressure of the castrated SHR (44 weeks) was significantly lower than those of intact SHR and testosterone-replaced SHR. The norepinephrine (NE) levels and the tyrosine hydroxylase (TH) activities in the abdominal aorta and mesenteric artery of castrated SHR (45-50 weeks) were significantly lower than those of intact SHR. The NE levels and the TH activities in these blood vessels of testosterone-replaced SHR recovered to the levels obtained in those of intact SHR. As well as the systolic blood pressure, the NE levels and TH activities in blood vessels of WKY were significantly lower than those of intact SHR and showed no significant difference among the three groups. These results suggest that androgen may contribute to the development of hypertension in SHR via sustained enhancement of TH activity in blood vessels leading to increased NE level.抄録全体を表示PDF形式でダウンロード (417K) -
Mayumi Mori, Hiromi Tsushima, Tomohiro Matsuda1994 年 66 巻 4 号 p. 445-450
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーThe effects of microinjection of purinoceptor agonists into the hypothalamic supraoptic nucleus (SON) on urination were examined in water-loaded and ethanol-anesthetized rats. Adenosine triphosphate (ATP), but neither adenosine diphosphate (ADP), adenosine monophosphate (AMP) nor adenosine, concentration-dependently decreased the urine outflow with concomitant increase in the urine osmotic pressure. The ED50 value for ATP was approx. 60 nmol. The antidiuretic effect of ATP was blocked either by prior injection of theophylline (an antagonist of the P1-type purinoceptor) or by intravenous administration of an arginine vasopressin (AVP)-receptor antagonist, d(CH2)5-D-Tyr(Et)-valine-arginine-vasopressin (VAVP). These results suggest that ATP injected into the SON has antidiuretic effects due to release of AVP through an activation of theophylline-sensitive purinoceptors.抄録全体を表示PDF形式でダウンロード (460K) -
Mari Tanaka, Norio Muto, Eiichi Gohda, Itaru Yamamoto1994 年 66 巻 4 号 p. 451-456
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーIn this study, the effect of ascorbic acid 2-glucoside (AA-2G), a stable derivative of ascorbic acid (AsA), or repeated additions of ascorbate on antibody productions by human peripheral blood lymphocytes (PBLs) was examined, and the physiological function of AsA was evaluated. When human PBLs were stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen, AA-2G remarkably increased the numbers of IgM- and IgG-secreting cells which were detected by enzyme-linked immunospot assay. Although a single addition of ascorbate was without effect, the effect of AA-2G was remarkably inhibited by the addition of castanospermine, an a-glucosidase inhibitor; and moreover, repeated additions of AsA to the culture medium during the culture period enhanced the response to the same level as did a single addition of AA-2G. These results indicate that AsA has the ability to stimulate the immunoglobulin productions by AA-2G. The phytohemagglutinin-induced proliferative response of PBLs was also stimulated by AA-2G. The intracellular AsA content in PBLs cultured with AA-2G was maintained at relatively high levels during the culture period, whereas the content with a single dose of AsA reached nearly zero by the end of the experiment. These in vitro findings suggest that AA-2G and AsA function as potent immunostimulators of antibody production in humans and that the intracellular AsA content is a key parameter for establishing the immune response of PBLs.抄録全体を表示PDF形式でダウンロード (423K) -
Hiroyuki Yoshida, Toshiaki Tamaki, Yasuharu Aki, Shoji Kimura, Ikumasa ...1994 年 66 巻 4 号 p. 457-464
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWe examined the effects of angiotensin II (Ang II) on isolated rabbit afferent arterioles to assess the direct effect of Ang II at the resistance vessel level in the kidney. We microdissected the superficial afferent arteriole from the kidney of New Zealand White rabbits. The afferent arteriole was cannulated with a micropipette system, and the intraluminal pressure was set at 80 mmHg. Ang II did not change the lumen diameter of the afferent arterioles. After the afferent arterioles were pretreated with aspirin DL-lysine or indomethacin, Ang II (10-7 M) caused transient vasoconstriction in the afferent arterioles. Ang II (10-7 M) caused persistent constriction in the afferent arterioles pretreated with NG-nitro-L-arginine (10-4 M). Physiological doses of Ang II decresed the lumen diameter of the isolated afferent arterioles pretreated with NG-nitro-L-arginine and aspirin DL-lysine. Dup753 (10-6 M), an AT1-receptor antagonist, abolished the vasoconstrictor effects of Ang II. These findings suggest that the isolated rabbit afferent arteriole has AT1 receptors, and the vasoconstrictor response of Ang II is counteracted by vasodilatory prostaglandins and nitric oxide.抄録全体を表示PDF形式でダウンロード (649K) -
Chiaki Kamei, Yukio Sugimoto1994 年 66 巻 4 号 p. 465-469
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーEffects of ions on histamine (Hi)-induced depolarization were studied in guinea pig adipocytes. Depolarization induced by Hi in guinea pig adipocytes was decreased by removal of K+ from the medium or pretreatment with ouabain at concentrations that showed no significant effect themselves. The decrease in membrane potentials induced by Hi was also abolished potently by replacement of Na+ by choline or pretreatment with tetrodotoxin at a concentration that caused no significant action alone. Pretreatment with monensin at a concentration lower than that eliciting the action resulted in a potentiation of Hi-induced depolarization. The depolarization induced by Hi was not affected by the presence of Ca2+ in the medium or pretreatment of the cells by diltiazem.抄録全体を表示PDF形式でダウンロード (266K) -
Katsuya Higo, Akira Karasawa1994 年 66 巻 4 号 p. 471-479
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーWe examined the effects of KW-3635, a thromboxane (TX) A2-receptor antagonist, and OKY-046, a TX synthetase inhibitor, on the prostaglandin (PG) I2 production in endothelium-intact and -injured guinea pig aorta and compared them with those of aspirin. In the endothelium-intact aorta, both the low (3 mg/kg) and the high (100 mg/kg) dose of aspirin similarly reduced the PGI2 production, as measured ex vivo 1 hr after the injury. In contrast, neither KW-3635 (10 mg/kg) nor OKY-046 (30 mg/kg) inhibited the PGI2 production. The endothelial injury, induced by balloon catheterization, caused a reduction of PGI2 production in the aorta and decline of plasma PGI2/TXA2 ratio. In the endothelium-injured animals, the high dose of aspirin further reduced the PGI2 production in the aorta, whereas KW-3635 and OKY-046 did not affect it. KW-3635 and OKY-046 also ameliorated the reduced ratio of PGI2/TXA2 in the plasma. The present results demonstrate that aspirin, but not KW-3635 or OKY-046, reduces the PGI2 production in the aorta either in the endothelium-intact or -injured state. It is thus suggested that the TXA2-receptor antagonist and the TX synthetase inhibitor have some advantages over aspirin when used for the prevention of acute thrombosis after percutaneous transluminal angioplasty.抄録全体を表示PDF形式でダウンロード (1127K) -
Shoichiro Shiraishi, Tomio Okamura, Atsumi Mori, Noboru Toda1994 年 66 巻 4 号 p. 481-488
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーIsolated dog internal thoracic arteries (ITA) responded to norepinephrine and phenylephrine with concentration-related contractions, which were suppressed by prazosin, but not by yohimbine. Clonidine did not contract ITA. In coronary arterial strips, norepinephrine produced a relaxation. Isoproterenol relaxed coronary arterial strips contracted with serotonin but did not alter the tone of ITA. Forskolin and beraprost, an analog of prostaglandin I2, relaxed coronary and ITA strips to a similar extent. The β-adrenoceptor density, assayed by [3H]dihydroalprenolol binding, was markedly less in ITA than in coronary arteries. Nicotine and transmural electrical stimulation did not alter the tension of ITA. Immunohistochemical study indicated that nerve fibers containing tyrosine hydroxylase immunoreactivity were markedly less in ITA than in coronary and mescnteric arteries. These results indicate that β-adrenoceptor function and adrenergic innervation are considerably reduced in dog ITA. Norepinephrine-induced vasocontraction appears to be mediated by α1-adrenoceptors in the arteries.抄録全体を表示PDF形式でダウンロード (612K) -
Kazuhiro Nakamura, Toshihiko Iijima1994 年 66 巻 4 号 p. 489-492
発行日: 1994年
公開日: 2006/04/10
ジャーナル フリーThe reason for the postnatal changes of action potential duration in rat heart cells is still a matter of controversy. We have examined mRNA expression levels of Kv1.2, one of the K+-channel genes, in neonatal (1 week) and adult (8 weeks) rat cardiac ventricles. For analysis of mRNA expression, we used the reverse transcription-polymerase chain reaction method. The level of Kv1.2 mRNA expression in adult rats was significantly higher than that in neonatal rats. This result suggests that the levels of ion channel gene expression may be responsible for the postnatal changes of the action potential duration.抄録全体を表示PDF形式でダウンロード (247K)
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