巻号一覧
80 巻 (1999)
- 4 号 p. 275-
- 3 号 p. 185-
- 2 号 p. 97-
- 1 号 p. 1-
80 巻, 4 号
選択された号の論文の15件中1～15を表示しています
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Reviews
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Takashi Sasamura, Yasushi Kuraishi1999 年 80 巻 4 号 p. 275-280
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーVanilloid receptor subtype 1 (VR1), a capsaicin receptor, is expressed in primary sensory neurons and vagal nerves. Heat and protons as well as capsaicin activate VR1 to induce the influx of cations, particularly Ca2+ and Na+ ions. Characteristic effects of capsaicin are the induction of a burning sensation after acute administration and the desensitization of sensory neurons after large doses and prolonged administration. The latter feature made capsaicin cream applicable for the treatment of chronic pain and pruritus. Capsaicin alters several visceral functions, which may be mediated by action on vagal nerves and central neurons. Capsaicin affects thermoregulation after intra-hypothalamic injection and releases glutamate from the hypothalamus and cerebral cortex slices, while VR1-like immunoreactivity is not apparent in these regions. These findings taken together suggest the existence of other subtypes of vanilloid receptors in the brain.抄録全体を表示PDF形式でダウンロード (810K) -
Soichi Miwa, Yasushi Iwamuro, Xiao-Feng Zhang, Taijiro Enoki, Yasuo Ok ...1999 年 80 巻 4 号 p. 281-288
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーThe contraction of the rat aorta induced by endothelin-1 (ET-1) requires entry of extracellur Ca2+, but involvement of voltage-operated Ca2+ channel is minor. Using whole-cell recordings of patch-clamp and monitoring of the intracellular free Ca2+ concentration ([Ca2+]i), we characterized Ca2+ entry channels in A7r5 cells activated by ET-1. ET-1 activates three types of voltage-independent Ca2+ entry channels: two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC). Furthermore, it was found that these channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. NSCC-1 is resistant to SK&F 96365, but sensitive to LOE 908, whereas NSCC-2 is sensitive to both SK&F 96365 and LOE 908. SOCC is sensitive to SK&F 96365, but resistant to LOE 908. Using these channel blockers, we analyzed Ca2+ entry channels involved in the ET-1-induced contractions of rat thoracic aorta and increases in [Ca2+]i of single smooth muscle cells. The responses to lower concentrations of ET-1 (≤0.1 nM) were abolished by either SK&F 96365 or LOE 908 alone. In contrast, the responses to higher concentrations of ET-1 (≥1 nM) were suppressed by SK&F 96365 or LOE 908 to about 10% and 35% of controls, respectively, and abolished by combined treatment with SK&F 96365 and LOE 980. These results show that the responses of rat aorta to lower concentrations of ET-1 involve only one Ca2+ channel that is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those to higher concentrations of ET-1 involve NSCC-1, NSCC-2 and SOCC, contributing 10%, 55% and 35%, respectively, to total Ca2+ entry.抄録全体を表示PDF形式でダウンロード (1111K)
Regular Papers
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Tristan Messager, Jean Michel de Bray, Pierre Jallet, Elmar Rump, Jean ...1999 年 80 巻 4 号 p. 289-294
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーThe exact mechanisms of cerebral arterial hypoxia are not perfectly defined. Our purpose is to adapt and validate, with drugs well known in rats and rabbits, a closed cranial window technique in gerbils. The method was used with seventeen gerbils to measure diameter changes of the pial arterioles under normoxia (after the topical application of agonists and antagonists of ATP-sensitive and Ca2+-dependent potassium channels), as well as under hypoxia. In normoxia, aprikalim (10-6 M), a direct activator of ATP-sensitive potassium channels, increases the diameter of pial arterioles by 10±2% (N=17). This effect is inhibited by glibenclamide (10-6 M), but not affected by iberiotoxin (10-6 M), a specific inhibitor of Ca2+-dependent potassium channels. The adenosine-induced dilation by 19±5% (N=17) is reduced by 59±16% with iberiotoxin, by 33±23% with glibenclamide and inhibited by theophylline (10-5 M). In hypoxia (15% O2), pial arteriole diameters are increased by 24±5% (N=17) and partially decreased by the application of glibenclamide and iberiotoxin to 59±11% and 54±5%, respectively. These data are similar to those obtained in other species and validate the closed cranial window technique on gerbils. They indicate that, as for rats and rabbits, both ATP-sensitive and Ca2+-dependent potassium channels are present in gerbil pial vessels and play a role in hypoxia.抄録全体を表示PDF形式でダウンロード (784K) -
Fumihiro Ohara, Toshiko Sugimoto, Nobuhiro Yamamoto, Kazumi Ohkubo, To ...1999 年 80 巻 4 号 p. 295-302
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーWe have studied the effects of FR168888 (5-hydroxymethyl-3-(pyrrol-1-yl)benzoylguanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in anesthetized rats and compared them with those of other cardioprotective compounds. FR168888 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes acidified with Na+-propionate with a Ki value of 6.4 nM. Pretreatment with FR168888 (0.032 - 0.32 mg/kg, i.v.) reduced or completely abolished the ventricular fibrillation (VF) induced by reperfusion after 5 min of regional ischemia, while lidocaine, a class I antiarrhythmic agent, showed less effect against VF as compared with FR168888. The size of myocardial infarction induced by 60-min ischemia and 60-min reperfusion was attenuated by FR168888 dose-dependently (1.0 - 10 mg/kg, i.v.), and ventricular tachycardia and VF were significantly reduced during the ischemic period. In contrast, propranolol and diltiazem did not show such protective effects on myocardial infarct size. In addition, FR168888 did not change hemodynamic parameters in rats. These results indicate that FR168888 has a strong inhibitory effect on Na+/H+ exchange and that treatment with FR168888 can protect the heart from arrhythmia and myocardial cell death in ischemic and reperfused situations.抄録全体を表示PDF形式でダウンロード (1134K) -
Takeshi Fujii, Shigeru Ohba, Katsuhiko Nakai, Kazuko Fujimoto, Takeshi ...1999 年 80 巻 4 号 p. 303-309
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーA possible involvement of serotonin-mediated cholinergic activation in the antidepressant effect of desmethylimipramine (DMI) was investigated by determination of the effects of a single or repeated DMI administration on acetylcholine (ACh) release in the hippocampus using an in vivo microdialysis technique and a radioimmunoassay for ACh. Rats were administered DMI (10 mg/kg, i.p.) acutely or repeatedly for 21 days. A single or repeated DMI administration did not cause any significant effects on the basal ACh release compared with the respective controls. Atropine perfusion in the acutely DMI-treated or control rats increased the ACh release to the same degree. In repeatedly DMI-treated rats, serotonin (5-HT) (1 to 10 μM) perfusion enhanced significantly the ACh release. However, 5-HT in acutely DMI-treated rats enhanced significantly the ACh release only at 10 μM. 5-HT did not cause any changes in ACh release in control rats. Hippocampal 5-HT content of acutely DMI-treated rats was significantly higher than that of saline-treated control rats, while no difference was observed between the repeatedly DMI- and saline-treated rats. These findings suggest, for the first time, that DMI induced a facilitation of cholinergic neurotransmission in the rat hippocampus through the activation of 5-HT-receptor function.抄録全体を表示PDF形式でダウンロード (1045K) -
Chiemi Sato, Yasumi Tsujioka, Takeshi Katsuragi1999 年 80 巻 4 号 p. 311-317
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーThe present study was designed to clarify the characteristics of contractions of guinea pig ileal longitudinal muscles evoked by α, β-methylene ATP as compared with those by other P2-agonists. α, β-Methylene ATP, ADP-β-S and 2-methylthio ATP as P2-agonists produced remarkable phasic contractions of the segment in a suramin-sensitive- and reactive blue-2-insensitive manner. However, ADP-β-S and 2-methylthio ATP, unlike α, β-methylene ATP, showed a biphasic contraction accompanied by a second sustained phase. Their second sustained contractions were notably suppressed by 30 μM reactive blue-2, probably being a component mediated by P2Y-purinoceptor. The phasic contractile response to α, β-methylene ATP, but not ADP-β-S and 2-methylthio ATP, was largely reduced by tetrodotoxin and atropine, indicating that the contraction is due to acetylcholine released from the cholinergic nerves. At 100 μM, α, β-methylene ATP inhibited the phasic contractions caused by a low concentration of itself, but not those induced by ADP-β-S and 2-methylthio ATP, presumably serving as a desensitizer of the P2-receptor. Although β, γ-methylene ATP per se showed little contraction, it prevented the contraction evoked by α, β-methylene ATP, but not those by ADP-β-S and 2-methylthio ATP. The contraction evoked by 100 μM 2-methylthio ATP was attenuated in the presence of ADP-β-S at 10 and 30 μM. From separate cross-interactions between two groups of P2-agonists, there seems to be different subtypes of P2X-purinoceptors in the pre- and postsynapse in producing phasic contractions, but not sustained contractions that are mediated by, presumably, the P2Y-purinoceptor of the ileum.抄録全体を表示PDF形式でダウンロード (771K) -
Motohiro Nishida, Kenji Sakamoto, Tetsuro Urushidani, Taku Nagao1999 年 80 巻 4 号 p. 319-325
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーl-cis Diltiazem, an optical isomer of diltiazem, protects against myocardial dysfunction in vitro, whereas its Ca2+ channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidence that l-cis diltiazem actually protects against ischemia/reperfusion injury in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 min. Treatment with diltiazem before and during ischemia (bolus 200 μg/kg and 15 μg/kg per minute for 25 min, i.v.; 575 μg/kg total) showed slightly depressed hemodynamic parameters, while l-cis diltiazem (1150 μg/kg) had no effect. Treatment with l-cis diltiazem produced a high recovery of the thickening fraction and limited the infarct size in a dose-dependent manner. Furthermore, the treatment with l-cis diltiazem (1150 μg/kg) or diltiazem (575 μg/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that l-cis diltiazem affects some events in the onset of reperfusion, independently of Ca2+-channel-blocking action. Our observations are the first to show that l-cis diltiazem demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.抄録全体を表示PDF形式でダウンロード (984K) -
Rosane Gomez, Nelson Asnis, Seminamis L. Tannhauser, Helena M.T. Barro ...1999 年 80 巻 4 号 p. 327-331
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーThis study described the effects of GABA agonists on glucose plasma concentrations of streptozotocin-induced diabetic rats. Low doses of an indirect GABA agonist, AOAA (aminooxyacetic acid); a GABAA and a GABAB agent, THIP (4, 5, 6, 7-tetrahydroisoxazolo[5, 4-c]pyridone) and baclofen, respectively; and a benzodiazepine were administered to non-diabetic and to diabetic rats. Plasma glucose concentrations were estimated during fasting and after an oral glucose load. Diazepam (1 mg/kg), baclofen (1 mg/kg) and AOAA (30 mg/kg), significantly decreased glycemia after oral glucose overload of streptozotocin-induced diabetes. None of the GABA-acting agents tested changed fasting or glucose overload glycemia of normal rats. Diazepam was the only drug to increase the fasting blood glucose concentration of diabetic rats. Treatment with AOAA or diazepam was accompanied by increased insulin plasma concentrations in diabetic rats to levels similar to the ones of non-diabetic animals. These results demonstrate that benzodiazepines and other GABA drugs act the endocrine pancreas in vivo, ultimately increasing plasma insulin and decreasing high blood glucose levels of diabetic rats. The acute and prolonged effects of the multitude of drugs acting on the GABAA-benzodiazepine-chloride ionophore complex remain to be broadly investigated as a therapeutic tool in diabetes.抄録全体を表示PDF形式でダウンロード (781K) -
Dan-Qiao Wang, Eiichi Kakizoe, Yuta Kobayashi, Keiko Shimoura, Hideki ...1999 年 80 巻 4 号 p. 333-342
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーRole of tissue angiotensin-converting enzyme (ACE) in the development of pressure-overload cardiovascular hypertrophy was examined in rats by comparing the inhibitory effect of trandolapril (high efficiency on tissue ACE) with that of enalapril (low efficiency) at equally antihypertensive doses. Rats with abdominal aorta banded or sham-operated were orally treated with trandolapril (0.5 mg/kg per day), enalapril (20 mg/kg per day) or vehicle for 8 weeks after the surgical maneuvers. In vehicle-treated rats, the banding raised the intra-aortic systolic pressure by 58%, diastolic pressure by 31%, maximum velocity of pressure rise by 65%, left ventricular (LV) weight by 41%, LV hydroxyproline concentration by 56%, aortic mass by 46%, LV ACE activity by 45%, and aortic ACE activity by 265%. Although both drugs equally reduced the aortic systolic pressure to approx. 70% and diastolic pressure to approx. 80% that of banded rats receiving vehicle, trandolapril partially prevented the LV hypertrophy, whereas enalapril yielded non-significant suppression. Trandolapril completely prevented the LV increments in hydroxyproline and ACE activity, whereas enalapril partially inhibited the LV hydroxyproline increase with little inhibition of LV ACE activity. In contrast, both inhibitors almost completely prevented the aortic hypertrophy, with the ACE activity of the aorta being potently inhibited. These results suggest that tissue ACE is the principal factor for pressure-induced aortic hypertrophy and an important yet non-essential factor for LV hypertrophy.抄録全体を表示PDF形式でダウンロード (1358K) -
Tomoaki Tokuno, Minoru Watanabe, Yuji Imaizumi1999 年 80 巻 4 号 p. 343-350
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーEffects of lactate on changes in intracellular pH (pHi) and contractility during simulated ischemia and reperfusion were examined in single myocytes of the guinea pig cardiac ventricle. The conditions of simulated ischemia were produced by the exchange of perfusion medium from the standard one oxygenated with 95% O2 - 5% CO2 gas (pH 7.4) to one containing no glucose, 8 mM K+, and 0 - 30 mM sodium-D, L-lactate and was gassed with 90% argon - 10% CO2 (pH 6.6). The pHi was decreased by the simulated ischemia from approx. 7.3 to approx. 6.9 regardless of lactate concentration, while the rate of pHi decrease was increased by lactate in a concentration-dependent manner. The contraction induced by electrical stimulation disappeared faster in the presence of lactate. The incidence of irreversible hypercontracture of myocytes was significantly reduced by 20 - 30 mM lactate. The overshoot of pHi to approx. 7.7 and excess contractions were induced by withdrawal of lactate during the reperfusion, but not observed when lactate was continuously present. The recovery of normal contractility during reperfusion was facilitated by lactate. It can be concluded that lactate added to or removed from the perfusion medium increases the rate of pHi change under the simulated ischemia and reperfusion, respectively, and that the continuous presence of lactate reduces cell injury under these conditions.抄録全体を表示PDF形式でダウンロード (1138K) -
Manami Kimura, Kouichi Katayama, Yukio Nishizawa1999 年 80 巻 4 号 p. 351-358
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーWe have examined the effect of glutamate receptor antagonists and voltage-dependent calcium channel blockers on the neuronal injury induced by the combination of a low concentration of N-methyl-D-aspartate (NMDA) or kainate and energy compromise resulting from the use of glucose-free incubation buffer. Toxicity induced by NMDA or kainate was enhanced in the glucose-free buffer. NMDAor non-NMDA-receptor antagonists added to the glucose-free buffer at the same time inhibited the neuronal cell death induced by each agonist. An NMDA-receptor antagonist, MK-801, but not non-NMDA-receptor antagonists, inhibited the toxicity when added to the culture medium after exposure of the cells to the agonists. P/Q-type calcium channel blockers, ω-agatoxin IVA and ω-agatoxin TK, and an N-type calcium channel blocker, ω-conotoxin GVIA, significantly attenuated the neuronal injury, although an L-type calcium channel blocker, nifedipine, showed little neuroprotective effect. A combination of calcium channel blockers of the three subtypes showed the most prominent neuroprotective effect. These observations suggest that the overactivation of NMDA and non-NMDA receptors and consequent activation of the voltage-dependent calcium channels lead to neuronal cell death in energy-compromised cortical neurons.抄録全体を表示PDF形式でダウンロード (1049K) -
Galen M. Pieper, Ching-San Lai1999 年 80 巻 4 号 p. 359-370
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーWe utilized the nitric oxide (NO) scavenger N-methyl-D-glucamine dithiocarbamate-Fe2+ (MGD-Fe) to characterize the role of NO in basal and acetylcholine (ACh)-stimulated relaxation arising from the endothelium of control vs diabetic rat aortic rings. In phenylephrine-contracted rings, MGD-Fe produced an additional increment in tension that was indomethacin-insensitive (i.e., excluding a role of prostanoids in this action). This MGD-Fe-sensitive component was more pronounced in control rings than diabetic rings and of the same magnitude achieved in rings without MGD-Fe treatment after removal of endothelium or treatment with the NO synthase inhibitor L-nitroarginine (L-NA). This suggests complete scavenging of basal NO by MGD-Fe and supports reduced basal NO in diabetic rings. ACh fully relaxed both control and diabetic rings. This relaxation was abolished by removal of the endothelium and was inhibited by L-NA (by 100% and 90% in control and diabetic rings, respectively). In contrast, MGD-Fe only partially inhibited ACh-induced relaxation in control (65±5% inhibition) and diabetic (41±11% inhibition) rings. The MGD-Fe-resistant component was not further modified by indomethacin. Addition of L-arginine (L-ARG) (but not D-arginine (D-ARG) enhanced the ACh-induced relaxation of MGD-Fe-treated diabetic (but not control) rings. These data provide evidence about endothelium-dependent relaxation in control and diabetic rings which cannot be discerned by use of L-NA alone. This study suggests that ACh produces a NO synthase-dependent vasodilation, a portion of which is due to free NO radical (·NO) or due to NO in a form or location that is unavailable for scavenging by MGD-Fe.抄録全体を表示PDF形式でダウンロード (1488K)
Short Communications
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Miki Shimada, Eriko Watanabe, Yuka Iida, Kiyoshi Nagata, Yasushi Yamaz ...1999 年 80 巻 4 号 p. 371-373
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーAdministration of an endotoxin, lipopolysaccharide (1 mg/kg body weight), caused decreases in hepatic sulfations of xenobiotics in male rats through changes in the amounts of at least three forms of sulfotransferases, ST1A1, ST1B1 and ST1C1. The time-dependent decrease was first observed with ST1B1, followed by ST1A1 and ST1C1; and the decrease was more profound in the levels of mRNAs than those of proteins. The decreases in their mRNAs were, however, prevented by the pretreatment with dexamethasone. These results suggest that the endotoxin suppresses the hepatic sulfation through a cytokine-mediated mechanism to change individually hepatic levels of ST1A1, ST1B1 and ST1C1.抄録全体を表示PDF形式でダウンロード (365K) -
Koji Tomiyama, Eisuke Nishio, Yasuhiro Watanabe1999 年 80 巻 4 号 p. 375-378
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーAs we reported previously, both wortmannin and lovastatin inhibit the differentiation in 3T3-L1 cells when these drugs were applied during the insulin-induced cell differentiation. In the present study, 3T3-L1 cells were treated with wortmannin and simvastatin after the completion of the insulin-stimulation, and differentiation was found to be significantly decreased by these drugs. This suggests intracellular signaling pathways play roles in the differentiation of 3T3-L1 cells even after the completion of the insulin-stimulation and also suggests that not only the early phase (day 0 to day 2) but also the late phase (day 2 to day 4) of differentiation is important for the differentiation of the cells.抄録全体を表示PDF形式でダウンロード (797K) -
Toru Egashira, Fusako Takayama, Yasumitsu Yamanaka, Yasuhiro Komatsu1999 年 80 巻 4 号 p. 379-382
発行日: 1999年
公開日: 2001/03/31
ジャーナル フリーThe Kampo medicine Sho-saiko-to scavenged superoxide anion radicals (O2-), hydroxyl radicals (·OH) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals in a dose-dependent fashion. We attempted to investigate the transition of free radical scavenging activity in plasma after oral administration of Sho-saiko-to in rats. From the response-time profile, kinetic parameters including values for Ka (absorption rate constant), Tmax (peak concentration time), T1/2 (half life) and MRT (mean residence time) of radical scavenging activity in plasma could be calculated for the O2-, ·OH and DPPH radicals. These parameters calculated from the dynamics of antioxidation are considered a very meaningful procedure to examine the effects of Sho-saiko-to.抄録全体を表示PDF形式でダウンロード (564K)
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