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Volume 81 (1999)
- Issue 4 Pages 317-
- Issue 3 Pages 253-
- Issue 2 Pages 125-
- Issue 1 Pages 1-
Volume 81, Issue 2
Displaying 1-16 of 16 articles from this issue
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Reviews
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Tangui Maurice, Vân-Ly Phan, Alexandre Urani, Hiroyuki Kamei, Yuk ...1999 Volume 81 Issue 2 Pages 125-155
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSNeuroactive neurosteroids, including progesterone, allopregnanolone, pregnenolone and dehydroepiandrosterone, represent steroid hormones synthesized de novo in the brain and acting locally on nervous cells. Neurosteroids modulate several neurotransmitter systems such as γ-aminobutyric acid type A (GABAA), N-methyl-D-aspartate (NMDA) and acetylcholine receptors. As physiologic consequences, they are involved in neuronal plasticity, learning and memory processes, aggression and epilepsy, and they modulate the responses to stress, anxiety and depression. The σ1-receptor protein was recently purified and its cDNA was cloned in several species. The amino-acid sequences are structurally unrelated to known mammalian proteins, but shared homology with a fungal sterol C8-C7 isomerase. The σ1-receptor ligands exert a potent neuromodulation on excitatory neurotransmitter systems, including the glutamate and cholinergic systems. Consequently, selective σ1 agonists show neuroprotective properties and beneficial effects in memory processes, stress and depression. The evidence of a direct interaction between neurosteroids and σ1 receptors was first suggested by the ability of several steroids to inhibit the binding of σ1-receptor radioligands in vitro and in vivo. A crossed pharmacology between neurosteroids and σ1-receptor ligands was described in several physiological tests and behavioral responses. This review will detail the recent evidence for a common mechanism of action between neurosteroids and σ1-receptor ligands and focus on the potential therapeutic interests of such interaction in the physiopathology of learning and memory impairments, stress, depression and neuroprotection.View full abstractDownload PDF (5173K)
Full Papers
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Keiko Takahashi, Mitsumasa Ohyanagi, Kiyomitsu Ikeoka, Tadaaki Iwasaki1999 Volume 81 Issue 2 Pages 156-162
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe extent to which reported abnormal responses of the human coronary circulation to acetylcholine in patients with hypercholesterolemia reflect endothelial injury is not clear. We used an in vitro rabbit model to determine whether these reactions involve endothelial or vascular smooth muscle dysfunction. Coronary resistance arterioles were isolated from hearts of rabbits fed 1% cholesterol to induce hypercholesterolemia or a control diet for 4 weeks. Arterioles were double cannulated with glass micropipettes and pressurized in a no-flow state. Acetylcholine contracted the arterioles in a concentration-dependent manner whether or not the nitric oxide synthase inhibitor NG-monomethyl-L-arginine was added. In control but not hypercholesterolemic preparations, contraction was significantly greater when endothelium was removed. In the hypercholesterolemic group, contraction significantly exceeded that in controls. In control but not high-cholesterol preparations, substance P dilated vessels with intact endothelium in a concentration-dependent manner. Addition of NG-monomethyl-l-arginine inhibited this response. With or without endothelium, norepinephrine contracted arterioles to a greater extent in the hypercholesterolemic group than in controls. We concluded that severe hypercholesterolemia decreased endothelially dependent factors by injuring endothelium and independently increased contractility of vascular smooth muscle.View full abstractDownload PDF (949K) -
Xiao-Ping Yang, Shigetoshi Chiba1999 Volume 81 Issue 2 Pages 163-169
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe present study demonstrated the progressive inhibition by prolonged cold storage (4, 7 and 14 days at 4°C) on prejunctional and postjunctional functions of purinergic and adrenergic components of double-peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated canine splenic artery. After the cold storage for 4 days, the first phase constriction was markedly decreased, whereas the second response was not significantly modified. Furthermore, after the 7 days of cold storage, the first phase was substantially depressed at low frequencies, but at high frequencies, a low level of contractile responses was still observed. On the other hand, the second phase in the cold stored artery for 7 days largely remained at any used frequencies. Moreover, the 14 days of cold storage almost completely inhibited the vasoconstrictor responses to nerve stimulation. Tyramine-induced constrictions were progressively decreased in the stored-days dependent manner, although the ATP and the noradrenaline-induced one was not modified for 4 and 7 days of the cold storage. In conclusion, 1) the 4°C cold stored artery for 4 days may show preferential injury of its tyramine-dependent noradrenaline releasing mechanisms, whereas nerve excited ones might well remain; and 2) the prejunctional contractile response of purinergic transmission might be damaged more preferentially than that of adrenergic transmission within 7 days storage.View full abstractDownload PDF (1809K) -
Kayoko Okuyama, Satoko Kiuchi, Masahito Okamoto, Hiroshi Narita, Yukit ...1999 Volume 81 Issue 2 Pages 170-175
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSOne of the most common acute complications of stroke is brain edema. Treatment of edema is recommended when the condition of the patients is deteriorating. The present study was undertaken to evaluate the effect of T-477 [(R)-(+)-2-(4-chlorophenyl)-2, 3-dihydro-4-diethyl aminoacetyl-4H-1, 4-benzothiazine hydrochloride], a novel neuronal Na+ and Ca2+ channel blocker, on brain edema in rats. Cerebral ischemia was induced by intra-arterial infusion of 1000 microspheres into the forebrain of freely moving rats, resulting in brain edema. T-477 was intravenously infused continuously for 24 h or twice for 3 h with a 3-h interval between infusions immediately after microsphere injection. T-477 dose-dependently inhibited the increase in brain water content by both infusion procedures; the inhibition was statistically significant at doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, infusion of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the decrease in K content and the increase in Ca content of the forebrain. In conclusion, T-477 prevents brain edema following microsphere-induced cerebral embolism in rats.View full abstractDownload PDF (766K) -
Koichi Nakayama, Yoshihisa Fukuta, Akihiko Kiyoshi, Yoshiyuki Iwatsuki ...1999 Volume 81 Issue 2 Pages 176-184
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSWe examined the binding of a 1, 4-dihydropyridine-sensitive Ca2+ channel ligand, (+)-[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (KATP) channel ligand, [3H]glyburide, to heart, lung and brain membranes isolated from Sprague-Dawley rats made pulmonary hypertensive by monocrotaline, a pyrrolizidine alkaloid. A single subcutaneous injection of monocrotaline increased right ventricular systolic pressure, a measure of pulmonary arterial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[3H]PN200-110 and [3H]glyburide binding site densities (Bmax) were reduced in hypertrophied right ventricles when normalized per unit protein in comparison with those of age-matched control (sham) rats, whereas the values of the dissociation constant (Kd) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [3H]PN200-110 binding to the lung membranes of the monocrotaline-induced pulmonary hypertensive rats was increased. The results indicate that the change in the binding of 1, 4-dihydropyridine Ca2+ and KATP channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.View full abstractDownload PDF (1187K) -
Yen-Mei Lee, Yen-Yen Peng, Jeon-Rong Sheu, Chen-Yu Cheng, Mao-Hsiung Y ...1999 Volume 81 Issue 2 Pages 185-193
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSATP-sensitive potassium (KATP) channel openers, exerting a potent vasodilatory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3, 4-trans-3, 4-dihydro-2, 2-dimethyl-2H-3-hydroxy4-[2-oxo-5S-(1-ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized KATP channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10 - 15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective KATP channel blocker. In conclusion, MJ-355, through the activation of KATP channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and/or acute myocardial infarction.View full abstractDownload PDF (1144K) -
Haruhisa Nishi1999 Volume 81 Issue 2 Pages 194-199
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSBoth extracellular adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP) induced corticoid production (steroidogenesis) concentration-dependently in bovine adrenocortical cells (BA cells). Pertussis toxin (PTX, approx. 2 μg/ml) partially inhibited (approx. 55% inhibition) extracellular ATP (100 μM)-induced steroidogenesis in BA cells. However, PTX did not inhibit extracellular UTP (100 μM)-induced steroidogenesis. Both ATP- and UTP-induced steroidogeneses were significantly inhibited by suramin (50 - 200 μM). These effects were inhibited significantly by reactive blue-2 (more than 100 μM) and pyridoxal-phosphate-6-azophenyl-2′, 4′-disulphonic acid (more than 100 μM). Both nucleotides (1 - 100 μM) induced inositol phosphates accumulation and intracellular Ca2+ mobilization, but PTX did not inhibit them. The RT-PCR procedure identified only P2Y2-receptor mRNA in BA cells. These results suggest that extracellular ATP induces steroidogenesis via a unique P2 receptor linked to PTX-sensitive guanine nucleotide-binding protein (G-protein), while extracellular UTP induces steroidogenesis via P2 receptor linked to PTX-insensitive G-protein. Thus, it was concluded that at least two different P2Y-like receptors linking to steroidogenesis exist in BA cells.View full abstractDownload PDF (843K) -
Kyoko Ichida, Masahiro Ikeda, Kuniyuki Goto, Katsuaki Ito1999 Volume 81 Issue 2 Pages 200-208
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSWe used the whole-cell clamp and fura-2 techniques to study the membrane current and intracellular Ca2+ concentration ([Ca2+]i) changes of mouse megakaryocytes in response to palytoxin (PTX), a highly potent marine toxin. At a holding potential of -60 mV, PTX induced a sustained inward current in a dose-dependent manner. The reversal potentials measured in the presence of various extracellular major cations indicated that the PTX-induced channel had a non-selective permeability to alkali metal ions. Although elimination of intracellular Ca2+ had no effect on the PTX-induced current, removal of external Ca2+ inhibited the current activation. During the sustained phase of the PTX-induced current, treatment with ADP activated an additional current. Pretreatment with ouabain, an inhibitor of Na+-K+-ATPase, suppressed the PTX-induced current. During the stable phase of the PTX-induced current, challenge with NiCl2 (5 mM) or 2, 4-dichlorobenzamil (DCB, 25 μM), a non-selective cation channel blocker, partially reversed the current. Simultaneous measurement of the membrane current and [Ca2+]i showed that PTX induced the current response without increasing the [Ca2+]i. Taken together, these results indicate that PTX induces a non-selective cation channel in mouse megakaryocytes. This channel is distinct from the ADP-operated channel and is sensitive to ouabain, NiCl2 and DCB.View full abstractDownload PDF (1163K) -
Masanobu Yoshikawa, Kouichi Yokogami, Ken Kitamura, Tomomi Kobayashi, ...1999 Volume 81 Issue 2 Pages 209-215
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe effect of phosphorothioated antisense oligodeoxynucleotide (AS ODN) against the μ-opioid receptor (MOR) on MOR mRNA level in the periaqueductal gray (PAG) of rat brain was investigated. The MOR mRNA levels at 3, 6, 12, 24, 48 and 72 h after MOR AS ODN microinjection into the PAG were determined by reverse transcriptase-polymerase chain reaction. The MOR mRNA level was significantly decreased only at 12 h after the injection of 10 μg MOR AS ODN. When 10 μg MOR AS ODN was given three times at the interval of 48 h, MOR mRNA levels were significantly decreased at 6, 12 and 24 h after the last injection of the AS ODN. However, MOR mRNA levels were not significantly changed by three injections at 48-h interval of MOR sense ODN or AS ODNs against δ- and κ-opioid receptors, although the two latter AS ODNs significantly reduced the respective targeted mRNA levels. In conclusion, the present results show that the selective decrease in MOR mRNA is at least one reason why the reported diminished effects of MOR agonists are produced in animals pretreated with MOR AS ODN, although they could be produced through several mechanisms in which MOR mRNA level does not change.View full abstractDownload PDF (1107K) -
Takashi Kosasa, Yuka Kuriya, Yoshiharu Yamanishi1999 Volume 81 Issue 2 Pages 216-222
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSDonepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer’s disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5 - 10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were ≤2.5, 10, 10 and ≤10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, ≤1; tacrine, 2; ENA-713, 4; TAK-147, ≤4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.View full abstractDownload PDF (944K) -
Ol’ga Pechánová, Misato Kashiba, Masayasu Inoue1999 Volume 81 Issue 2 Pages 223-229
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe present study examined the role of glutathione in the development of hypertension induced by long-term inhibition of nitric oxide (NO)-synthase. Three groups of rats were investigated: control group, L-NAME group: group with NO-synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg per day) for 2 weeks, and BSO group: group with glutathione synthesis inhibitor L-buthionine sulfoximine (BSO, 1.4 mmol/kg per 12 h) for 3 days. All the groups were subjected to an acute i.v. experiment in which the given substances were exchanged between groups. There was no change in systolic blood pressure (SBP) in the control group after 1 and 2 h of acute BSO (1.4 mmol/kg, i.v.) treatment. In the L-NAME group, SBP increased significantly by 10% after 2 h of acute BSO treatment. In the BSO group, SBP did not change vs control; however, after 2 h of acute L-NAME (10 mg/kg, i.v.) treatment, the increase in SBP exceeded by 12% (P<0.05) that of the control group. Along with the increase in SBP, acute BSO treatment significantly potentiated the decrease in plasma nitrite/nitrate concentration in the L-NAME group. The acute BSO-induced glutathione decrease was significantly greater in the L-NAME group than in the control group. In NO-deficient hypertensive rats, the results are indicative of a decrease in glutathione synthesis and a stabilizing role of glutathione.View full abstractDownload PDF (770K) -
Masumi Yoshida, Kazuhide Inaguma, Mikio Ito1999 Volume 81 Issue 2 Pages 230-236
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSIn the present study, we investigated the susceptibility to restraint plus water-immersion stress (RWIS) in rats with daunomycin-induced nephrosis in comparison to that in normal rats. The severity of RWIS-induced gastric lesions was significantly less in nephrotic rats on the 20th and 40th days after a single i.v. injection of daunomycin (12 mg/kg) than in the respective control rats. Acid secretion in pylorus-ligated rats significantly decreased under the 3-h stress. On the 20th day after treatment with daunomycin, acid secretion was significantly less in nephrotic rats than in control rats under both stress and unstressed conditions. Pretreatment of normal rats with methylene blue, a guanylate cyclase inhibitor, or phenylephrine, a vasoconstrictor, significantly prevented the stress-induced gastric lesions and decreased acid secretion. Nω-Nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor, prevented the stress-induced gastric lesion formation only. These results indicate that nephrotic rats are more resistant to RWIS-induced gastric lesions than normal rats. In addition, these results suggest that the decrease in acid secretion related to the decrease in the release of NO from endothelial cells may contribute, at least in part, to the prevention of the stress-induced gastric lesion formation in nephrotic rats.View full abstractDownload PDF (845K)
Short Communications
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Satoru Suzuki, Masayoshi Furushiro, Masatoshi Takahashi, Masashi Sakai ...1999 Volume 81 Issue 2 Pages 237-239
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSMongolian gerbils orally administered with soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS, 240 mg/kg) for 5 days were subjected to cerebral ischemia by bilateral common carotid artery occlusion. The pyramidal cell damage of the hippocampal CA1 subfield was classified into 4 grades according to the proportion of damaged neurons on the tenth day after the ischemic treatment. The damage score of the SB-tPS group was statistically less than that of the control group. This suggests that the pre-administration of SB-tPS may relieve the delayed neuronal cell death caused by cerebral ischemia.View full abstractDownload PDF (647K) -
Norimichi Nakahata, Toshiko Yaginuma, Yasushi Ohizumi1999 Volume 81 Issue 2 Pages 240-243
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSSince maitotoxin, a potent marine toxin, is known to cause not only Ca2+ influx but also phosphoinositide hydrolysis, we investigated the Ca2+ dependency of maitotoxin-induced phosphoinositide hydrolysis in 1321N1 human astrocytoma cells. Maitotoxin elicited inositol 1, 4, 5-trisphosphate accumulation in a time-dependent manner. In [3H]inositol-labeled cells, maitotoxin stimulated phosphoinositide hydrolysis in an extracellular Ca2+-dependent manner. Maitotoxin also caused an intracellular Ca2+ elevation, which was abolished by an intracellular Ca2+ chelater BAPTA-AM. Interestingly, maitotoxin still caused phosphoinositide hydrolysis in the BAPTA-AM-treated cells. These results indicate that maitotoxin-induced phosphoinositide hydrolysis is dependent on extracellular but not intracellular Ca2+ in 1321N1 human astrocytoma cells.View full abstractDownload PDF (449K) -
Minoru Mitsuda, Masahiro Nomoto, Shin-ichi Iwata1999 Volume 81 Issue 2 Pages 244-246
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSEffects of β-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as “points”, which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. β-Blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.View full abstractDownload PDF (438K) -
Toshihiko Kuro, Yutaka Kobayashi, Masanori Takaoka, Yasuo Matsumura1999 Volume 81 Issue 2 Pages 247-251
Published: 1999
Released on J-STAGE: March 31, 2001
JOURNAL FREE ACCESSThe effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), a novel Na+/Ca2+ exchange inhibitor, on ischemic acute renal failure (ARF) in rats were examined. ARF was induced by clamping the left renal pedicle for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was markedly diminished in ARF rats. Pretreatment with KB-R7943 (10 mg/kg, i.v.) markedly attenuated the ARF-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damage, which was suppressed by KB-R7943. Activation of the reverse mode of Na+/Ca2+ exchange seems to play an important role in the pathogenesis of ARF. A selective Na+/Ca2+ exchange inhibitor may be useful in cases of ARF.View full abstractDownload PDF (821K)
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