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Volume 72 (1996)
- Issue 4 Pages 261-
- Issue 3 Pages 195-
- Issue 2 Pages 83-
- Issue 1 Pages 1-
Volume 72, Issue 4
Displaying 1-12 of 12 articles from this issue
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Katsutoshi Goto, Hiroshi Hama, Yoshitoshi Kasuya1996 Volume 72 Issue 4 Pages 261-290
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSSince the discovery of the most potent vasoconstrictor peptide, endothelin, in 1988, explosive investigations have rapidly clarified much of the basic pharmacological, biochemical and molecular biological features of endothelin, including the presence and structure of isopeptides and their genes (endothelin-1, -2 and -3), regulation of gene expression, inttacellular processing, specific endothelin converting enzyme (ECE), receptor subtypes (ETA and ETB), intracellular signal transduction following receptor activation, etc. ECE was recently cloned, and its structure was shown to be a single transmembrane protein with a short intracellular N-terminal and a long extracellular C-terminal that contains the catalyiic domain and numerous N-glycosylation sites. In addition to acute contractile or secretory actions, endothelin has been shown to exert long-term proliferative actions on many cell types. In this case, intracellular signal transduction appears to converge to activation of mitogen-activated protein kinase. As a recent dramatic advance, a number of non-peptide and orally active receptor antagonists have been developed. They, as well as current peptide antagonists, markedly accelerated the pace of investigations into the true pathophysiological roles of endogenous endothelin-1 in mature animals; e.g., hypertension, pulmonary hypertension, acute renal failure, cerebral vasospasm, vascular thickening, cardiac hypertrophy, chronic heart failure, etc. Thus, the interference with the endothelin pathway by either ECE-inhibition or receptor blockade may provide an exciting prospect for the development of novel therapeutic drugs.View full abstractDownload PDF (2388K) -
Tatsuro Yokoyama, Kazuo Ichihara, Yasushi Abiko1996 Volume 72 Issue 4 Pages 291-297
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSEffect of efonidipine, a long-acting dihydropyridine derivative, on the endothelin-1 (ET-1)-induced coronary vasoconstriction was studied in open-chest anesthetized dogs. Efonidipine (0.03 or 0.1 mg/kg) was administered i.v. 10 min before an intracoronary injection of ET-1 (30 pmol/kg). An intracoronary injection of ET-1 decreased coronary blood flow (CBF) that was measured by a flow probe. The ET-1-induced decrease in CBF was sustained for more than 30 min without significant changes in blood pressure and heart rate. Pretreatment with efonidipine attenuated the decrease in CBF induced by ET-1 significantly and dose-dependently. ET-1 also reduced coronary diameter for more than 30 min as evaluated by the coronary angiography technique. Pretreatment with efonidipine also attenuated the reduction in coronary diameter induced by ET-1 significantly and dose-dependently. These effects of efonidipine were sustained for at least 30 min after the ET-1 administration. It is concluded that efonidipine attenuates the ET-1-induced vasoconstriction, and therefore the drug would be useful for some patients with variant angina, in which ET-1 is involved in the genesis of coronary vasoconstriction.View full abstractDownload PDF (443K) -
Kazuho Abe, Hiroshi Saito1996 Volume 72 Issue 4 Pages 299-306
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe examined the effect of menadione on the morphology and viability of cultured astrocytes. Exposure of astrocytes to menadione induced a progressive cell death. The toxic effect of menadione was concentration- and time-dependent. Menadione toxicity was blocked by antioxidants, superoxide dismutase, catalase and iron chelators, indicating that superoxide anions (02¯), hydrogen peroxide (H202) and hydroxyl radicals (''OH) are all involved in menadione toxicity. Menadione cyiotoxicity should be useful as a model for studying the mechanisms underlying oxidative injury in the brain and for the screening of drugs that may attenuate cell damage caused by oxidative stress.View full abstractDownload PDF (463K) -
Hiroki Teraoka, Ryo Takai, Tetsuro Taneike, Takeo Hiraga, Akira Ohga1996 Volume 72 Issue 4 Pages 307-315
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe uptake and release properties of Ca2+ by several subcellular fractions of the bovine adrenal medulla were investigated. Investigation by the 45Ca2+ tracer method showed that permeabilized cells and the fractions of mitochondria (MT) and microsomes (MC) caused ATP-dependent Ca2+ uptake in a Ca2+ concentration-dependent manner (pCa 8-4), whereas permeabilized cells and the fractions of secretory granules (SG) were able to accumulate a significant amount of Ca2+ even in the absence of ATP, which was completed by the addition of hexokinase and glucose. In these organelle fractions, Ca2+ uptake in the presence of ATP at pCa 7 and pCa 5.8 was well-correlated with the activity of the NADPH cyiochrome c reductase (marker enzyme for the endoplasmic reticulum) and cytochrome c oxidase (marker enzyme for mitochondria), respectively. As detected by Fura-2 ratiometry, both inositol 1, 4, 5-trisphosphate (IP3) and caffeine caused concentration-dependent Ca2+ releases from permeabilized cells and MC, but not from MT and SG. In an ATP-depleted condition, homogenates still took up a significant amount of Ca2+ but was not able to respond to IP3 and caffeine. These results suggest that the endoplasmic reticulum is a major Ca2+-storing organelle, which releases Ca2+ in response to IP3 and caffeine in bovine adrenal chromaffin cells.View full abstractDownload PDF (617K) -
Haruo Kobayashi, Tadahiko Suzuki, Yoshinori Kasashima, Akira Motegi, I ...1996 Volume 72 Issue 4 Pages 317-324
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSTriorganotin compounds like tributyltin have been reported to be biodegraded to diorganotin, monoorganotin and then inorganic tin in animals after they have been ingested. Effects of tributyltin, dibutyltin and monobutyltin on various cholinergic parameters that are involved in synaptic transmission in the mouse cerebral cortex were investigated in vitro. Tributyltin and dibutyltin, but not monobutyltin, inhibited the activity of choline acetyltransferase, both the high-affinity and low-affinity uptakes of choline into synaptosomes, and the binding of [3H]quinuclidinyl benzilate to muscarinic acetylcholine receptors. Tributyltin and dibutyltin, but not monobutyltin, had a slightly suppressive effect on the K+-induced release and synthesis of acetylcholine in slices of the cortex. A11 three butyltins at concentrations from 10−6 to 10&, inus;4M had no effect on the activity of acetylcholinesterase. The extent of the inhibitory effects on the cholinergic parameters, apart from the activity of acetylcholinesterase, was slightly greater in the case of tributyltin than dibutyltin, in particularly at the highest concentration (10−4M) tested. Therefore, it is concluded that tributyltin metabolites inhibit various parameters of cholinergic activity with a potency ranking of tributyltin > dibutyltin > monobutyltin.View full abstractDownload PDF (705K) -
Hideo Kurosawa, Hiroshi Narita, Minako Kaburaki, Hideo Yabana, Hisayos ...1996 Volume 72 Issue 4 Pages 325-333
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSInfluence of cardiotonic agents on the prognosis of heart failure depends on the individual therapeutic agents, and favorable and unfavorable effects of these agents have been reported in clinical trials. We studied the effect of the cardiotonic agent denopamine on the life span of cardiomyopathic hamsters (BIO 14.6 strain) in the heart failure period. Non-treated hamsters started to die at 40 weeks of age, and their survival rate decreased to 23.8% at the age of 65 weeks. Hamsters treated with denopamine (400 ppm in diet) from 36 weeks of age did not die until the age of 52 weeks, except in cases of accidental death. The survival rate of this group at 65 weeks of age was about 40%. Survival rates of these 2 groups were significantly different (P<0.05) when animals with accidental death were excluded. To elucidate the mechanism of the effect of denopamine, we performed several experiments after dietary treatment with denopamine for 4 to 6 weeks from 37 weeks of age. Denopamine treatment lowered plasma levels of noradrenaline and dopamine (P<0.05), but affected neither the cardiac contractility nor the β-adrenoceptor density. In summary, denopamine significantly decreases the mortality of cardiomyopathic hamsters. Its effect to lower the plasma catecholamine levels may be responsible for the beneficial effect of denopamine.View full abstractDownload PDF (632K) -
Norio Sakai, Hisamitsu Ujihara, Kumatoshi Ishihara, Masashi Sasa, Chik ...1996 Volume 72 Issue 4 Pages 335-346
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSA patch clamp study was performed to determine which subtype of ionotropic glutamate receptors is involved in the glutamate-induced excitation of the medial vestibular nucleus (MVN) neurons. Whole cell recording was performed on MVN neurons that were acutely dissociated by enzymatic and mechanical treatments. Application of glutamate at a concentration of 100 μM produced a current with a reversal potential of approximately O mV. The glutamate-induced current was completely blocked by 6-cyan0-7-nitroquinoxaline-2, 3-dione (CNQX, 10μM), a non-N-methyl-D-aspartate (NMDA)-receptor antagonist. Application of α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainic acid (KA), non-NMDA-receptor agonists, at concentrations of 30 and 100 μM produced a concentration-dependent depolarization concomitantly with an increase in firing rates during current clamp recording. During voltage clamp recording, glutamate, AMPA and KA elicited a concentration-dependent current with an equilibrium potential of approximately O mV. To clarify whether NMDA receptors are present in MVN neurons, the effects of glycine on the glutamate- and NMDA-induced current were examined. Two types of NMDA receptor-mediated current (types1 and 2) were obtained in terms of the difference in sensitivity to both magnesium ion and MK-801, which act on the NMDA-receptor channel. In the type I neurons, the NMDA-induced current was not apparently blocked by magnesium ion or MK-801, although a larger current was obtained in the absence of magnesium ion. In the type 2 neurons, marked blockade of the NMDA-induced current was seen in the presence of magnesium ion and MK-801, as previously reported in other neurons of the central nervous system. These findings indicate the presence of both non-NMDA and NMDA receptors, which are involved in primary afferent transmission, in the MVN neuron, and two distinct types of NMDA receptors.View full abstractDownload PDF (714K) -
Yosuke Murata, Toshio Matsuda, Kazuko Tamada, Rie Hosoi, Shoichi Asano ...1996 Volume 72 Issue 4 Pages 347-353
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSOuabain markedly stimulated not only [3H]thymidine incorporation but also [3H]uridine incorporation into astrocytes. The effects were observed at 36-48 hr and 12-72 hr after addition of ouabain, respectively. The dose-response curves were both bell-shaped types with a peak at 10−3 M for thymidine incorporation and 2 × 10−3 M for uridine incorporation. Ouabain increased cell number as determined by an assay using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and by a method using a hemocyiometer. Low concentration of external K+ mimicked the effect of ouabain in stimulating [3H]-thymidine incorporation, and high concentration of external K+ blocked the effect of ouabain. In contrast to astrocyies, ouabain did not stimulate [3H]thymidine incorporation into C6 glioma and fibroblast cells. The effect of ouabain on [3H]thymidine incorporation in astrocyies was dependent on external Ca2+, and it was blocked by cycloheximide. These findings indicate that prolonged Na+, K+-ATPase inhibition causes cell proliferation in cultured astrocyies in cell-specific and Ca2+-dependent manners.View full abstractDownload PDF (466K) -
Ryuji Nagai, Shinya Nagata1996 Volume 72 Issue 4 Pages 355-364
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe effective combination of C + + and assembler could realize real-time power spectral analysis of various fluctuation indexes simultaneously. The blood pressure (BP) waveform indexes (WIs) analyzed simultaneously were heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP). Power amplitudes (very low frequency, VLFamp; low frequency, LFamp; and high frequency, HFamp) were evaluated by accurate BP waveform recognition, accurate automatic rejection of outliers, baseline adjustment in periodograms and digital filtering of each amplitude. In the in vivo experiments, the amplitudes were changed in a dose-dependent manner by methylatropine (HR-VLFamp, HR-LFamp and HR-HFamp), phentolamine (HR-LFamp, SBP-VLFamp, SBP-LFamp and SBP-HFamp) and propranolol (HR-LFamp and SBP-LFamp). The absolute correlation coefficients of the amplitude and the change in each parameter were more than 0.96. In conclusion, this real-time, noise-adjusted power spectral analysis system for investigating HR and BP fluctuations enabled us to accurately evaluate autonomic nerve activity in conscious rats. Moreover, unlike other systems, this system was able to detect the biphasic changes in SBP-HFamps caused by phentolamine.View full abstractDownload PDF (545K) -
Hiroshi Shiga, Shigeki Miyake, Norio Fukuda, Ryosuke Yorikane, Hiroyuk ...1996 Volume 72 Issue 4 Pages 365-374
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe antianginal effect of RS-5773 ((2S, 3S)-3-acetoxy-8-benzyl-2, 3-dihydro-5-[2-(dimethylamino)-ethyl]-2-(4-methoxyphenyl)-1, 5-benzothiazepine-4-(5H)-one hydrochloride), a newly developed benzothiazepine derivative, was evaluated in an angina model rat. Close-coronary artery injections of methacholine in anesthetized rats evoked ischemic electrocardiographic (ECG) changes (S wave elevation of about 0.6 mV). The ECG changes produced by methacholine were reproducible for as long as 6 hr. Intravenous and intraduodenal administration of RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the ischemic ECG changes. RS-5773 exceeded the other two agents both in the maximum suppressive effect on S wave elevation and in the duration of action after intravenous administration. The antianginal potency expressed as AUC (area under the curve), i.e., the percent suppression of S wave elevation integrated over time, revealed that RS-5773 was 16 times and 7 times more potent than diltiazem and clentiazem, respectively. A similar order of potency difference was observed after intraduodenal administration, and RS-5773 sustained its effect for about 6 hr at 3 mg/kg. In addition, RS-5773 did not cause excessive hypotension or depression of atrioventricular conduction. These results suggest that RS-5773 has a preferable profile as an antianginal agent.View full abstractDownload PDF (616K) -
Hiroyuki Iizuka, Yoko Watanabe, Shuji Kojima1996 Volume 72 Issue 4 Pages 375-379
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSSince oxidative modification of low-density lipoprotein (LDL) and uptake of the oxidized LDL by macrophages are closely related to the pathogenesis of atherosclerosis, we examined the inhibitory effect of 5, 6, 7, 8-tetrahydroneopterin (NPH4) on Cu(II)-induced lipid peroxidation of LDL. NPH4 significantly inhibited both lipid peroxidation and the associated increase of electrophoretic mobility of ApoB protein. Furthermore, NPH4 suppressed the uptake of oxidized [14C]oleyl-esterified LDL by the macrophage-like cell line J774. NPH4 may be a candidate for the treatment of atherosclerosis and other active oxygen-related diseases.View full abstractDownload PDF (387K) -
Yasuo Oyama, Eisuke Okazaki, Lumi Chikahisa, Takayuki Nagano, Chiharu ...1996 Volume 72 Issue 4 Pages 381-385
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSIn order to study the oxidative stress-induced change in intracellular concentration of Ca2+ ([Ca2+]i) and Ca2+-induced oxidative stress, effects of hydrogen peroxide and ionomycin, a calcium ionophore, on rat cerebellar neurons were examined using a flow cytometer and fluorescent dyes: fluo-3 for monitoring [Ca2+]i; 2'', 7''-dichlorofluorescin, for reactive oxygen species; and 5-chloromethylfiuorescein, for cellular nonprotein thiols. Oxidative stress induced by hydrogen peroxide dose-dependently increased [Ca2+]i and decreased the content of nonprotein thiols. Ionomycin increased oxidative metabolism and decreased the content of nonprotein thiols. Results suggest that oxidative stress induces an increase in [Ca2+]j While an increase in [Ca2+]i increases oxidative stress in neurons.View full abstractDownload PDF (341K)
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