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Volume 80 (1999)
- Issue 4 Pages 275-
- Issue 3 Pages 185-
- Issue 2 Pages 97-
- Issue 1 Pages 1-
Volume 80, Issue 2
Displaying 1-13 of 13 articles from this issue
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Reviews
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Shokei Kim, Hiroshi Iwao1999 Volume 80 Issue 2 Pages 97-102
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSExtracellular signal-regulated kinases (ERKs) and c-jun NH2-terminal kinases (JNKs), which belong to the family of mitogen-activated protein kinases (MAPKs), play a key role in the regulation of cell growth or apoptosis or various gene expressions. In spite of the critical importance of MAPKs for cell function in vitro, the role of MAPKs in the pathophysiology of the cardiovascular system in vivo is poorly understood. Recently, we have examined the activities of MAPKs in various cardiovascular disease models. JNKs activity is chronically enhanced in cardiac hypertrophy of hypertensive rats or angiotensin II-infused rats, which is followed by the increase in activator protein-1 (AP-1) activity composed of c-Fos and c-Jun proteins. In chronic hypertensive rats, vascular ERKs and JNKs activities are continuously increased compared with normotensive rats, with the development of vascular thickening. Furthermore, balloon injury rapidly and transiently activates vascular ERKs and JNKs, followed by the activation of AP-1. This activation of ERKs and JNKs in injured artery is in part mediated by angiotensin AT1 receptor. Thus, the enhanced activation of JNKs or ERKs occurs in various cardiovascular disease models, supporting the notion that MAPKs may be a useful target for treatment of cardiovascular hypertrophy and remodeling.View full abstractDownload PDF (755K) -
Nobuyuki Kuramoto, Kiyokazu Ogita, Yukio Yoneda1999 Volume 80 Issue 2 Pages 103-109
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSc-Myc family proteins, encoded by c-myc family proto-oncogenes, play critical roles in mechanisms associated with proliferation, differentiation and apoptotic death in eukaryotic cells. These functions are mediated by transcriptional activity of these proteins through binding to the E-box core sequence CACGTG referred to as a Myc core element located at a promoter or enhancer region of the individual target genes in the nucleus. Recent studies have demonstrated the presence of novel nuclear proteins that specifically recognize a Myc core element, in addition to c-Myc, Max, Mad and Mxi1. On the other hand, a Myc core element has alternating purine/pyrimidine repeats which could undergo a conformational transition from right-handed (B-DNA) to left-handed (Z-DNA) forms in the presence of a high concentration of salts such as Mg2+ and polyamines. Similarly, a Myc element has a homopurine-homopyrimidine site that may take a triplex configuration in particular situations. We have searched for nuclear proteins that can specifically recognize a Myc core element in different topological variations in murine brain.View full abstractDownload PDF (897K)
Regular Papers
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Toyoshi Umezu1999 Volume 80 Issue 2 Pages 111-118
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThis study examined effects of various psychoactive drugs on the Vogel conflict test, where drinking behavior is punished by electric shocks, in ICR mice to clarify the pharmacological features of this method in mice. A benzodiazepine anxiolytic diazepam and a barbiturate pentobarbital produced significant anticonflict effects, which mean that these drugs increased the number of electric shocks mice received during 40-min test session. On the other hand, yohimbine (α2-receptor antagonist), caffeine (adenosine-receptor antagonist), scopolamine (muscarinic cholinergic antagonist), cyclazocine (σ-receptor antagonist), cimetidine (H2-receptor antagonist), baclofen (GABAB-receptor agonist), MK-801 (NMDA-receptor antagonist), buspirone (5-HT1A-receptor agonist), chlorpromazine (dopamine-receptor antagonist) and haloperidol (dopamine-receptor and σ-receptor antagonist) all did not produce anticonflict effects in this test using ICR mice. The results suggest that the Vogel conflict test is applicable to ICR mice and that this test in mice is appropriate as a screening method for drugs that have apparent anti-anxiety actions.View full abstractDownload PDF (968K) -
Yoshihiro Waki, Ken-ichi Miyamoto, Shinya Yamamoto, Yukie Saitoh, Shoh ...1999 Volume 80 Issue 2 Pages 119-125
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSWhen Walker 256/S carcinosarcoma (W256/S) was subcutaneously inoculated into the back of mature female Wistar Imamichi rats (10-week-old), the tumor grew rapidly and caused increases in the urinary excretions of calcium and hydroxyproline, without changes in the serum concentrations of calcium and inorganic phosphorus. Furthermore, osteoporosis-like changes in the femurs and decrease in uterus weight were observed, as previously reported for W256/S-bearing young rats. In the healthy mature female rats, the estrus cycle passed through four stages (proestrus, estrus, metestrus and diestrus) within 4 to 5 days, with a peak of serum estradiol and progesterone levels in the proestrus stage. On the other hand, after subcutaneous inoculation of W256/S into the rats, the estrus cycle tended to pause upon the metestrus or diestrus stage, accompanied with significantly low estradiol and progesterone levels in serum. W256/S tumor produced and secreted luteinizing hormone-releasing hormone (LH-RH). In conclusion, it seems that the ectopical secretion of LH-RH from the tumor resulted in the decrease in the secretion of gonadotropic hormones, following low level of sex hormones and stopping the estrus cycle. Therefore, W256/S-bearing rats may be a model for osteoporosis of hypoovarianism or postmenopause.View full abstractDownload PDF (794K) -
Young-Tso Lin, Bin-Nan Wu, Chiou-Fenq Horng, Yeun-Chih Huang, Show-Jen ...1999 Volume 80 Issue 2 Pages 127-136
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSIsoeugenolol (1.0, 3.0, 5.0 mg/kg, i.v.) produced a dose-dependent bradycardia and a decrease in blood pressure in anesthetized Wistar rats. Isoeugenolol inhibited the tachycardia effects induced by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by (-)phenylephrine. In isolated guinea pig tissues, isoeugenolol antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects on the atria and tracheal relaxations in a concentration-dependent manner. The apparent pA2 values for isoeugenolol on right atria, left atria and trachea were 7.63±0.03, 7.89±0.12 and 6.12±0.05, respectively, indicating that isoeugenolol was a highly selective β1-adrenoceptor blocker. On the other hand, isoeugenolol produced a mild direct cardiac depression at high concentration and was without intrinsic sympathomimetic activity (ISA). In isolated rat thoracic aorta, isoeugenolol relaxed more potently the contractions induced by (-)phenylephrine (10 μM) and 5-HT (10 μM) than those by high K+ (75 mM). In isolated guinea pig trachea, isoeugenolol attenuated the carbachol (1 μM)-contracted trachea more significantly than those contracted with high K+. Furthermore, the binding characteristics of isoeugenolol and various β-adrenoceptor antagonists were evaluated in [3H]CGP-12177 binding to rat ventricle, lung and interscapular brown adipose tissue (IBAT) membranes. The -log IC50 values of isoeugenolol for predominate β1-, β2- and β3-adrenergic receptor sites were 5.82±0.09, 4.74±0.05 and 4.73±0.12, respectively. In conclusion, isoeugenolol was found to be a highly selective β1-adrenoceptor antagonist with tracheal and vascular smooth muscle relaxant activities, but was devoid of α-adrenoceptor-blocking action.View full abstractDownload PDF (1377K) -
Kazufumi Kubota, Mikie Kubota-Watanabe, Kenji Fujibayashi, Koji Saito1999 Volume 80 Issue 2 Pages 137-142
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSIn neonatal rats, nociceptive responses induced by capsaicin were characterized pharmacologically. Capsaicin, injected subcutaneously (s.c.), induced body movement including scratching and struggling responses, and the responses were quantified by using a device composed of an audio speaker as a detector. The capsaicin-induced body movement was inhibited by a tachykinin NK1-receptor antagonist RP-67580 with an ID50 value of 3.5 mg/kg, s.c. Opioid analgesics, morphine, buprenorphine and pentazocine, also inhibited the body movement with ID50 values of 0.085, 0.0079 and 0.92 (mg/kg, s.c.), respectively. Non-steroidal anti-inflammatory drugs, indomethacin, ibuprofen and acetaminophen, did not exert any effect on the capsaicin-induced body movement. Neither the sedative diazepam nor the sedative chlorpromazine inhibited the body movement. It is concluded that the capsaicin-induced body movement in neonatal rats, which is considered to be nociceptive responses mediated by substance P, is sensitive to centrally acting analgesics with μ-opioid receptor agonist activity.View full abstractDownload PDF (741K) -
Hitoshi Kontani, Masumi Jinkawa, Chisato Shiraoya, Akiko Nagashima1999 Volume 80 Issue 2 Pages 143-153
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe effects of KRN2391 (N-cyano-N'-(nitroxyethyl)-3-pyridine carboximidamide methanesulfonate), which possesses ATP-sensitive potassium (K+) channel opening (KCO) activity and nitrate activity; Ki1769 (N-cyano-N'-(phenylethyl)-3-pyridinecarboximidamide methanesulfonate), which possesses only KCO activity; and nitroglycerin (NG) were determined on the motility of the ureter, urinary bladder and urethra of rats. Bladder contraction was induced by infusion of fluid into the bladder of conscious rats and recorded on a cystometrogram. KRN2391 and Ki1769 (both 0.3 mg/kg, i.v.) prolonged the micturition interval immediately after the injection, but NG (5 mg/kg, i.v.) did not. Peristaltic movement of the ureter, recorded in anesthetized rats, was inhibited by i.v. injection of KRN2391 and Ki1769 (both 0.03 mg/kg). However, when NG, NaNO2, N-nitro L-arginine methylester and methylene blue were applied directly to the ureter, no change in movement of the ureter was detected. KRN2391 (0.03 mg/kg, i.v.) and Ki1769 (0.3 mg/kg, i.v.) reduced the resistance to fluid infusion through the urethral lumen in anesthetized rats, whereas NG (0.5 mg/kg, i.v.) only reduced this resistance transiently. These results indicate that KCO activity had an inhibitory effect on the motility of the ureter, bladder and urethra. On the other hand, nitrate activity had an inhibitory effect on urethral tonus, corresponding to that induced by KCO activity.View full abstractDownload PDF (1347K) -
Ko Takakura, Ikunobu Muramatsu1999 Volume 80 Issue 2 Pages 155-161
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSTo investigate whether the nitrergic nerve-mediated smooth muscle relaxation is caused by authentic nitric oxide (NO) and is mediated via guanosine 3':5'-cyclic monophosphate (cyclic GMP), we compared the response to electrical field stimulation of nitrergic nerve (EFS) with other NO-related responses in rat gastric fundus strips. EFS, sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and acidified NaNO2 and inducible NO synthase (iNOS)-mediated NO all produced relaxation and elevated cyclic GMP level in rat fundus strips. However, the basal and stimulated cyclic GMP levels were significantly lower than the basal level in aorta (40±4 pmol/g wet tissue). Methylene blue and 6-anilino-5, 8-quinolinedione (LY83583), both known as soluble guanylyl cyclase inhibitors and O2- generators that scavenge NO, reduced the elevation of cyclic GMP level by all stimuli and inhibited the relaxations only in response to NaNO2 and iNOS-mediated NO but not to the other stimuli. These results suggest that in the rat gastric fundus strips the relaxations induced by not only nitrergic nerve but also SNP and SNAP are not associated with cyclic GMP production, in contrast to the relaxations mediated by authentic NO.View full abstractDownload PDF (854K) -
Tsutomu Yonehana, Munekazu Gemba1999 Volume 80 Issue 2 Pages 163-167
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSWe studied the effects of adenosine on injury caused by hypoxia and reoxygenation in LLC-PK1 cells. Lactate dehydrogenase and γ-glutamyltranspeptidase were released from cells exposed to hypoxia for 6 hr and then reoxygenation for 1 hr. The addition of adenosine at 100 μM to the medium before hypoxia began significantly decreased enzyme leakage into medium during both hypoxia and reoxygenation. The adenosine A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), at the concentration of 100 μM, did not affect enzyme release, but the adenosine A2-receptor agonist 2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosine hydrochloride (CGS 21680) at the concentration of 100 nM, suppressed the injury caused by hypoxia and reoxygenation. There were decreases in cAMP contents and ATP levels in LLC-PK1 cells injured by hypoxia and reoxygenation. Adenosine (100 μM) restored ATP levels in the cells during reoxygenation. With adenosine, the intracellular cAMP level was increased prominently during reoxygenation. These results suggest that adenosine protects LLC-PK1 cells from injury caused by hypoxia and reoxygenation by increasing the intracellular cAMP level via adenosine A2 receptor.View full abstractDownload PDF (690K)
Short Communications
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Ryo Saito, Kouichi Handa, Seigo Tanaka, Ai Fukumitsu, Kenji Honda, Yuk ...1999 Volume 80 Issue 2 Pages 169-172
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSElectrical field stimulation (EFS) caused biphasic relaxation, first transient and then sustained, of rat mesenteric arteries precontracted by prostaglandin (PG) F2α. The transient relaxation was reduced about 45%, and the sustained relaxation was not observed after endothelium denudation of the arteries. Nω-Nitro-L-arginine (L-NOARG) inhibited the biphasic relaxation induced by EFS. At 1 - 100 μM, L-NOARG inhibited the transient relaxation more than the sustained relaxation. Methylene blue inhibited the biphasic relaxation and at 100 μM, L-NOARG abolished the transient relaxation. These results suggest that the transient relaxation mainly involves nitric oxide (NO), whereas the sustained relaxation involves both NO and some other factor(s).View full abstractDownload PDF (419K) -
Katsuyuki Miura, Michiaki Okumura, Shinya Yamanaka, Shokei Kim, Hirosh ...1999 Volume 80 Issue 2 Pages 173-176
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSDirect effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 μg·kg-1·min-1), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect.View full abstractDownload PDF (462K) -
Shunichi Shimizu, Masako Yasuda, Masakazu Ishii, Tsutomu Nagai, Yuji K ...1999 Volume 80 Issue 2 Pages 177-180
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThis study examined whether tetrahydrobiopterin (BH4) stimulates angiogenesis by measuring the formation of tube-like structures in vascular endothelial cells. Bovine aortic endothelial cells that were cultured between two layers of collagen type I gel formed tube-like networks. Addition of BH4 or sepiapterin, a precursor of BH4 synthesis, stimulated the formation of tube-like structures. The sepiapterin-stimulated tube formation was completely inhibited by co-treatment with N-acetylserotonin, an inhibitor of sepiapterin reductase. These findings show that BH4 stimulates in vitro angiogenesis in vascular endothelial cells.View full abstractDownload PDF (473K) -
Jun-ichi Kiraku, Tetsuya Nakamura, Takao Sugiyama, Naoyuki Takahashi, ...1999 Volume 80 Issue 2 Pages 181-183
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSWe studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.View full abstractDownload PDF (375K)
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