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Volume 61 (1993)
- Issue 4 Pages 267-
- Issue 3 Pages 157-
- Issue 2 Pages 75-
- Issue 1 Pages 1-
Volume 61, Issue 3
Displaying 1-16 of 16 articles from this issue
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Manabu Amano, Arata Goto, Norimitsu Takahashi, Takaaki Hasegawa, Toshi ...1993 Volume 61 Issue 3 Pages 157-163
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe protective effects of BMY-21502 (1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4piperidinyl]methyl]-2-pyrrolidinone)against cerebral anoxia were investigated using various models in mice, in comparison with those of other cerebroactive drugs. Oral administration of BMY-21502 (10-100 mg/kg)significantly prolonged the survival time in KCN (2.4 mg/kg, i.v.)-induced anoxia. Oxiracetam and idebenone exerted similar but weak protection at doses above 100 mg/kg, p.o. and only at a dose of 100 mg/kg, p.o., respectively. Significant protection by BMY-21502 against moderate hypobaric hypoxia was observed at doses of 30 and 100 mg/kg, p.o. Idebenone (100 and 300 mg/kg, p.o.)significantly prolonged the survival time of mice in this model, but oxiracetam (30-300 mg/kg, p.o.)did not. Oral administration of all of these drugs (BMY-21502, 3 300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg)failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model. The anti-anoxic effect of BMY-21502 in the KCN-anoxia model was blocked by pretreatment with scopolamine. These findings suggest that BMY-21502 has an anti-anoxic action superior to those of the other cerebroactive drugs used, and activation of the CNS cholinergic system is involved as one of the causative mechanisms for the anti-anoxic effect of BMY-21502.View full abstractDownload PDF (445K) -
Minori Mitsui, Asaki Abe, Masaomi Tajimi, Hideaki Karaki1993 Volume 61 Issue 3 Pages 165-170
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe movement of a fluorescent intracellular Ca2+ indicator, fura-2, in smooth muscle was examined. Strips of rat and rabbit aortas and bovine trachea were loaded with the acetoxymethyl ester of fura2 (fura-2/AM), followed by washing with normal physiological solution. Not only fura-2/AM but also fura-2 was detected in the washout solution. The amount of fura-2 in the cells, measured fluorometrically, decreased gradually during the washout. The decrease was fastest in rat aorta followed by rabbit aorta > bovine trachea. In rat aorta, fura-2 leakage was inhibited by an inhibitor of anion transport, probenecid, or by a decrease in bath temperature. The Ca2+ ionophore ionomycin (10 μM)increased the leakage of fura-2, which was not inhibited by probenecid, possibly because a high concentration of ionomycin nonselectively increased membrane permeability. These results suggest that fura-2/AM is cleaved to fura-2 in the cell which gradually leaked out of the cell mainly by an anion transport system. The amount of fura-2 in the cell seemed to be determined mainly by the rate of leakage of fura-2, which is the largest in rat aorta followed by rabbit aorta and bovine trachea.View full abstractDownload PDF (411K) -
Toshimasa Fujiwara, Shigetoshi Chiba1993 Volume 61 Issue 3 Pages 171-176
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe stainless steel cannula inserting method was used to observe vascular effects of α-adrenoceptor agonists, phenylephrine (PE), methoxamine (ME), clonidine (CL)and xylazine (XY), on the isolated, perfused rabbit common carotid, renal and femoral arteries. PE and ME induced a dose-dependent vasoconstriction that was readily suppressed by treatment with bunazosin, an α1-adrenoceptor blocker. CL induced a constriction only in common carotid arteries, and this was readily suppressed by bunazosin. In preparations preconstricted by phenylephrine, CL and XY dose-dependently induced vasodilations in the 3 types of arteries, and these vasodilations were not modified by a potent α2-adrenoceptor antagonist, midaglizole. In preparations preconstricted by prostaglandin F2α, CL and XY did not produce any significant vasodilation, but CL induced a vasoconstriction in common carotid arteries that was completely blocked by bunazosin. Thus, it is concluded that: 1)α1-adrenoceptors are functionally predominant in rabbit peripheral arteries, 2)the α2-adrenoceptor agonist-induced vasodilation may be due to an antagonistic action towards α1-mediated constrictions, and 3)clonidine has α1-adrenoceptor stimulating properties in rabbit common carotid artery but not in renal and femoral arteries.View full abstractDownload PDF (415K) -
Naoyuki Takasugi1993 Volume 61 Issue 3 Pages 177-182
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSParticipation of calcium-induced vasodilation (due to an increase in synthesized nitric oxide (NO)content in endothelial cells)in the arterio-venous circulation, including the vascular bed was investigated by the vessel perfusion method in the isolated rabbit ear preparation. The perfusion medium used was a tris-buffered solution. When CaCl2 (6.25, 12.5 and 25 mg)was injected in the perfused vessel of the rabbit ear preparation, dose-dependent vasocontraction was observed when vascular tone was kept at a normal level. However, CaCl2 dose-dependently induced vasodilation of the vessel when it was continuously contracted by norepinephrine (1.2 × 10-7 M). This calcium-induced vasodilation was inhibited in the presence of NG-nitro-L-arginine (5 × 10-5M), a selective inhibitor of NO synthesis, and methylene blue, a guanylate cyclase inhibitor, although it was rarely affected by indomethacin (10-5 M), a cyclooxygenase inhibitor. Calcium-induced vasodilation was also obtained in the in situ circulation containing vascular bed, and this suggests that the vasodilation was due to a Ca2+-induced increase in the synthesis of NO derived from endothelial cells.View full abstractDownload PDF (361K) -
Noriyoshi Teramoto1993 Volume 61 Issue 3 Pages 183-195
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSEffects of semotiadil on the voltage-dependent Ca current (ICa)were investigated in dispersed smooth muscle cells of the rabbit portal vein. At a holding potential of -100 mV, semotiadil (≥0.1 μM; dissolved in dimethylsulphoxide, DMSO)inhibited the ICa in a concentration-dependent manner (IC50=2.0 μM, Hill''s coefficient = 1.0). At a holding potential of -80 mV or -60 mV, the concentration-inhibition curve observed in the presence of semotiadil was shifted to the left compared with that observed at -100 mV; and semotiadil shifted the voltage-dependent inactivation curve to the left. The curve for the decay of ICa was fitted with two time constants. Semotiadil (< 1 μM)reduced the slow but not the fast time constant. The curve for the recovery from ICa inactivation also consisted of two time constants, and semotiadil (1 μM)prolonged the slow recovery. Semotiadil dissolved in deionized water more potently inhibited ICa than semotiadil dissolved in DMSO. At pH 10.0, semotiadil did not modify the voltage-dependent inactivation curve. However, recovery from the inactivation was much faster at pH 10.0 than at pH 7.3. These results indicate that the voltage-dependent inhibition of Ica by semotiadil may be due to binding of the ionized drug during the inactivated state and also inhibition of the transition from the inactivated to the resting state. Long-lasting inhibition of ICa after removal of semotiadil may be due to tight binding of semotiadil on the channel through a hydrophobic site.View full abstractDownload PDF (923K) -
Tohru Masukawa, Yoshihiro Tochino1993 Volume 61 Issue 3 Pages 197-201
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe cerebral resistance to hypoxia in mice was investigated by measuring the survival time under both hypobaric and normobaric hypoxic conditions. In the ad libitum fed mice, there was a circadian variation in the survival time that was longer during the light period than during the dark period under hypobaric hypoxic conditions. The survival time under normobaric hypoxic conditions also exhibited a similar circadian variation in the ad libitum fed mice, whereas the rhythm of the survival time was completely reversed by the restriction of food presentation (9:00-15:00). These findings suggest that there is a circadian rhythm in the cerebral resistance of mice to hypoxia, which can be shifted by the time of food presentation. Furthermore, regression analyses revealed a negative correlation between the survival time of mice exposed to hypoxia and body temperature, and blood glucose levels. These indicate that the cerebral resistance to hypoxia was intimately associated with body temperature and blood glucose that both show a circadian rhythm in mice.View full abstractDownload PDF (291K) -
Mayumi Mori, Toshio Kamiya, Hiromi Tsushima, Tomohiro Matsuda1993 Volume 61 Issue 3 Pages 203-208
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe employed a brain microdialysis method to examine the possible regulation of spontaneous acetylcholine (ACh)release in the hypothalamic vasopressinergic supraoptic nucleus (SON)of rats. We monitored the basal ACh release in the SON-microdialysate. The addition of tetrodotoxin (10-6 M)to the perfusate (saline containing 10-4 M physostigmine)decreased the basal ACh release. A muscarinic receptor antagonist, atropine (non-selective)or pirenzepine (M1-selective), increased the basal ACh release in a concentration-dependent manner. The maximal increase occurred at 20-40 min after the start of the infusion of antagonists. The ED50 values for the stimulatory effects of atropine and pirenzepine were 9.4 × 10-8 and approx. 10-4 M, respectively. The effect of atropine (10-6 M)was inhibited by simultaneous addition of the muscarinic agonist oxotremorine (10-5 M). The results showed a negative feedback regulation of the spontaneous ACh release through the activation of muscarinic receptors in the SON. The weak effect of pirenzepine in increasing the ACh release, compared with atropine, suggests that ACh release in the nucleus is mainly regulated by the non-M1-muscarinic receptor subtype.View full abstractDownload PDF (457K) -
Osami Sakamoto, Hiroshi Mori, Kiyoyuki Kitaichi, Akihide Koda1993 Volume 61 Issue 3 Pages 209-220
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSPreviously, we reported that two novel 5-fluoropyrimidine derivatives, 2'', 3'', 5''-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21)and 1-{6-[N-(2-n-propyl-n-pentanoyl)glycyl]aminon-hexylcarbamoyl}-5-fluorouracil (UK-25), show potent antitumor activity with low immunotoxicological effects. The purpose of this paper was to evaluate the effect of these drugs on delayed type hypersensitivity (DTH). Not only UK-21 and UK-25 but also tegafur (FT-207)and 5-fluorouracil (5-FU)produced no suppression of picryl chloride (PC)-induced DTH in mice but rather enhanced it. It is known that variation of the sensitizing antigen dose alters the effect of drugs on the immune response. Because it was difficult to control the antigen dose in PC-DTH, the sheep erythrocyte (SRBC)-induced response was used to examine the effect of drugs on delayed type hypersensitivity in the succeeding experiments. Either a therapeutic dose or an over-dose of the respective drug was given to mice sensitized with 5 × 105 or 5 × 107 SRBC. The suppressive effects of UK-21 and UK-25 on the DTH were lower than those of FT-207 and 5-FU. UK-21 and UK-25 enhanced Meth A tumor-specific DTH in BALB/c mice, but FT-207 and 5-FU did not. UK-21, UK25 and FT-207 showed a tendency to enhance or restore the Meth A tumor neutralizing activity of spleen cells in mice bearing the tumor, but carmofur (HCFU)did not. These results indicated that the suppressive effects of UK-21 and UK-25 on the tumor immune response were also low.View full abstractDownload PDF (758K) -
Shinji Inukai, Mitsuji Agata, Manami Sato, Akira Naitou, Hidehiko Mats ...1993 Volume 61 Issue 3 Pages 221-227
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSTAT {[5-(3-thienyl) tetrazol-1-yl]acetic acid} is a novel aldose reductase (AR) inhibitor. It exhibited highly potent inhibition of partially purified AR from rat lens (IC50=2.1 × 10-8 M), rabbit lens (IC50 =2.3 × 10-8 M)and human placenta (IC50=2.8 × 10-8 M). On the other hand, TAT had a weak inhibitory activity against mouse liver aldehyde reductase (ALR)(IC50=2.4 × 10-6 M)and poor inhibitory activity against several adeninenucleotide-requiring enzymes. Against rat lens AR, TAT exhibited an uncompetitive inhibition at a concentration of 1.0 × 10-8 M and a mixed type inhibition at higher concentrations. TAT inhibited sorbitol accumulation in the isolated rat sciatic nerve (IC50=1.0 × 10-6 M), rat lens (IC50=5.7 &tomes; 10-6M), human erythrocytes (IC50=2.5 × 10-7 M), and rabbit erythrocytes (IC50=2.1 × 10-7 M) incubated with high glucose concentrations. The oral administration of TAT (5 -100 mg/kg/day) to streptozotocin (STZ)-induced diabetic rats during a 5-day treatment period decreased the sorbitol content in the sciatic nerve, dose-dependently (ED50: 8.8 mg/kg/day for the prevention and 9.0 mg/kg/day for the reversal). Moreover, TAT (2.5-40 mg/kg/day)improved the decreased motor nerve conduction velocity (MNCV) after a 14-day treatment period. There was a significant correlation between MNCV and sciatic nerve sorbitol content. From these results, TAT is expected to be useful for the clinical treatment of diabetic complications.View full abstractDownload PDF (393K) -
Kazuo Watanabe, Shingo Yano, Masayuki Yamamoto, Shoko Kanaoka1993 Volume 61 Issue 3 Pages 229-236
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the effects of cimetidine and famotidine on the acid secretory response to electrical vagal stimulation, bethanechol and histamine in the isolated mouse whole stomach preparation. The acid secretion elicited by electrical vagal stimulation at the position of the esophagus (10 Hz, 0.3 msec, 10 V for 5 min)was reproducible by repeated stimulation in each preparation, and it was abolished by tetrodotoxin, atropine and hexamethonium. This vagally stimulated acid secretion was abolished by cimetidine (3 mM), while it was only partly inhibited by famotidine (10-100 μM). Histamine (100 μM)-induced acid secretion was inhibited by cimetidine and famotidine, and the doses of these drugs required for complete inhibition were 3 mM and 10 μM, respectively. In contrast, bethanechol (10 μM)-induced acid secretion was slightly reduced by famotidine (1-100 μM), but markedly reduced by cimetidine (3 mM). In the guinea pig ileum, millimolar concentrations of cimetidine and famotidine shifted the dose-response curve of the contractile response to acetylcholine rightward. These findings suggest that the inhibitory effect of cimetidine on the vagally stimulated or bethanechol-induced acid secretion is elicited at least partly through mechanisms different from H2-antagonism.View full abstractDownload PDF (544K) -
Shogo Tokuyama, Masakatsu Takahashi, Hiroshi Kaneto1993 Volume 61 Issue 3 Pages 237-242
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSBesides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic)neurons in the fear and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25, 130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (±)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25, 130, but not by (±)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA.View full abstractDownload PDF (378K) -
Shoichiro Shiraishi, Atsumi Mori, Noboru Toda1993 Volume 61 Issue 3 Pages 243-250
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe endothelium-dependency of vasodilator responses was compared in helical strips of canine internal thoracic (ITA)and coronary arteries partially contracted with serotonin. The addition of acetylcholine produced a concentration-related relaxation in ITA and coronary arterial strips with an intact endothelium. The relaxations were not influenced by indomethacin, but were markedly inhibited or abolished by methylene blue, NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and endothelial denudation. The responses to low concentrations of acetylcholine were significantly greater in ITA than in coronary arteries, whereas relaxations induced by substance P, Ca2+ ionophore (A23187)or NO in ITA were significantly less. The substance P-induced relaxation in ITA and coronary arteries was endotheliumdependent, and it was almost abolished by L-NA. Relaxations induced by ATP in ITA were abolished by endothelium denudation and treatment with L-NA. In the coronary arteries, relaxing responses were inhibited only partially by removal of endothelium and L-NA. Acetylcholine, ATP and substance P relax canine ITA possibly by a mediation of endothelium-derived NO, but not prostaglandin I2 Coronary arterial relaxations induced by ATP appear to be mediated by an indirect action via NO released from the endothelium, in addition to a direct action on the smooth muscle.View full abstractDownload PDF (480K) -
Hideaki Mizumoto, Akira Karasawa1993 Volume 61 Issue 3 Pages 251-253
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe mechanism of the diuretic action of KW-3902 (8-(noradamantan-3-yl)-1, 3-dipropylxanthine), an adenosine A1-receptor antagonist, was investigated by a lithium clearance study and stop-flow method in anesthetized rats. KW-3902 increased urine volume (UV), sodium excretion and renal clearances of sodium (CNa)and lithium (CLi), when UV and CNa increased more than CLi- KW-3902 did not affect the stop-flow pattern, whereas trichlormethiazide inhibited the reabsorption of water and sodium at the distal nephron. These results suggest that the adenosine A1-receptor blockade exhibits diuretic effects via the inhibition of reabsorption of water and sodium mainly at the proximal tubule. The additional small contribution of the distal action can not be ruled out.View full abstractDownload PDF (212K) -
Yoshiaki Tabuchi, Yoichi Kurebayashi1993 Volume 61 Issue 3 Pages 255-257
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of ebselen (2-phenyl-1, 2-benzisoselenazol-3(2H)-on), a metal-containing organic compound, on gastric secretion and gastric ulceration were examined in rats. Intraduodenal ebselen (30 to 300 mg/kg)significantly and dose-dependently inhibited gastric secretion in pylorus-ligated rats. Both aspirin and water-immersion restraint stress-induced ulcers were significantly prevented by oral administration of ebselen at doses equivalent to the antisecretory doses. These results indicate that the antisecretory effect of ebselen underlies its antiulcer effect in these models.View full abstractDownload PDF (230K) -
Hidenari Sakuta, Koichi Okamoto, Yasuhiro Watanabe1993 Volume 61 Issue 3 Pages 259-262
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSEffects of sodium nitroprusside, 8-bromo cGMP and methylene blue on the glibenclamidesensitive K+ current evoked by K+ channel openers in Xenopus oocytes were studied. Sodium nitroprusside (0.1-1 mM, an activator of guanylate cyclase)enhanced by 20-50% the K+ currents induced by KRN2391, nicorandil and cromakalim (K+ channel openers). 8-Bromo cGMP (1 mM)also increased the K+ current by 40-60%. Methylene blue (10 μM, an inhibitor of guanylate cyclase)irreversibly blocked the K+ current by about 20-30%. These results suggest that the activation of glibenclamide-sensitive K+ channels by K+ channel openers is modulated either positively or negatively by intracellular cGMP in oocytes.View full abstractDownload PDF (252K) -
Satomi Adachi-Akahane, Yukiko Amano, Ryo Okuyama, Taku Nagao1993 Volume 61 Issue 3 Pages 263-266
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSA quaternary derivative of diltiazem (quat-DTZ)was tested to determine whether diltiazem approaches L-type Ca2+ channels from the outside or inside of the cell membrane. In single ventricular myocytes, both extra and intracellular application of quat-DTZ effectively blocked the L-type Ca2+ channel current, whereas D890 was effective only when applied intracellularly. These results strongly suggest that diltiazem binds to the channel from the outside as well as the inside of the membrane in a manner different from that of phenylalkylamines.View full abstractDownload PDF (213K)
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