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Volume 71 (1996)
- Issue 4 Pages 273-
- Issue 3 Pages 187-
- Issue 2 Pages 89-
- Issue 1 Pages 1-
Volume 71, Issue 4
Displaying 1-14 of 14 articles from this issue
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Eisuke Okazaki, Lumi Chikahisa, Kaori Kanemaru, Yasuo Oyama1996 Volume 71 Issue 4 Pages 273-280
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe effect of hydrogen peroxide (H2O2) on the intracellular Ca2+ concentration ([Ca2+]i) of rat thymocytes was examined by a flow cytometer and two fluorescent dyes, fluo-3-AM and ethidium bromide, a dye impermeant to intact membranes, to characterize the H2O2-induced increase in [Ca2+]i. H2O2 at concentrations greater than 30 μM dose-dependently increased the [Ca2+]i, of thymocytes which were not stained with ethidium. Removal of external Ca2+ greatly reduced the degree of H2O2-induced increase in [Ca2+]i. However, H2O2 still increased the [Ca2+]i under the external Ca2+-free condition. Diethylmaleate, which is known to produce a chemical depletion of cellular nonprotein thiol, significantly increased the [Ca2+]i. Dithiothreitol, which is used to protect cellular nonprotein thiol, slightly decreased the [Ca2+]i, but greatly reduced the H2O2-induced increase in [Ca2+]i. Therefore, it is considered that H2O2 may increase the [Ca2+]i through a mechanism related to the effects of H2O2 on the cellular nonprotein thiol.View full abstractDownload PDF (503K) -
Hideo Inoue, Nobuyuki Nagata, Shoji Shibata, Yasuko Koshihara1996 Volume 71 Issue 4 Pages 281-289
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe examined the effect of glycyrrhetinic acid (Ia) and its derivatives on ear edema induced by topical application of capsaicin in mice. Three dihemiphthalate compounds: di-sodium salt of 18β-olean12-ene-3β, 30-diol (deoxoglycyrrhetol, IIa) di-O-hemiphthalate (IIb); 18β-olean-9(11), 12-diene-3β, 30-diol di-O-hemiphthalate (IIIa); and olean-11, 13(18)-diene-3β, 30-diol di-O-hemiphthalate (IVa) inhibited capsaicin-induced edema with ED50 values of 52.6, 41.0 and 51.8 mg/kg (p.o.), respectively. However, glycyrrhetinic acid and deoxoglycyrrhetol at a dose of 200 mg/kg (p.o.) had no effect. Compound IIIa (100 mg/kg, p.o.) also inhibited the edema response to capsaicin in mast cell-deficient mice. Furthermore, compounds IIb, IIIa and IVa (25—100 mg/kg, p.o.) prevented ear edema in response to intradermal injection of substance P (SP) and compound 48/80. In addition, these compounds at a high dose of 100 mg/kg (p.o.) produced a significant inhibition of the plasma extravasation in ear skin induced by i.v. administration of SP. The above results suggest that the effect of these compounds on capsaicin-induced ear edema is due at least in part to an inhibition of the increase of vascular permeability induced by vasoactive agents released from mast cells. Moreover, it seems likely that these compounds at a high dose can suppress vasodilatation and plasma extravasation induced by SP involved in capsaicin-induced edema.View full abstractDownload PDF (1060K) -
Shinichiro Goto, Toru Egashira, Yuji Wada, Fusako Takayama, Yasumitsu ...1996 Volume 71 Issue 4 Pages 291-298
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated the in vitro effects of fluvoxamine on 3H-paroxetine binding and 3H-monoamine uptake in monkey cerebral cortex in comparison with those of other antidepressants. Fluvoxamine selectively inhibited 3H-5-hydroxytryptamine (5-HT) uptake and 3H-paroxetine binding. However, it did not alter 3H-norepinephrine or 3H-dopamine uptake. In addition, we examined the effects of chronic treatment with fluvoxamine (5 mg/kg per day, p.o.) on 5-HT uptake sites that bind 3H-paroxetine and 5-HT2 receptors that bind 3H-ketanserin, in monkey brains and platelets. Chronic treatment with fluvoxamine affected neither the paroxetine binding sites nor the kentanserin binding sites of the brains and platelets. These results suggest that long-term treatment with fluvoxamine does not affect either the 5-HT uptake sites or 5-HT2-receptors of 5-HT neurons in monkey brain in spite of its strong inhibitory effect on 5-HT uptake in vitro.View full abstractDownload PDF (541K) -
Lumi Chikahisa, Yasuo Oyama, Eisuke Okazaki, Katsuhiko Noda1996 Volume 71 Issue 4 Pages 299-305
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe have developed a procedure to simultaneously estimate cell viability and the cellular level of nonprotein thiol (presumably glutathione) using two fluorescent dyes, 5-chloromethylfluorescein (5CMF) and ethidium, and rat thymocytes. Diethylmaleate and N-ethylmaleimide reduced, respectively, the intensity of 5CMF fluorescence to 0.23 and 0.1, relative to the control. Incubation with buthionine sulfoximine, an inhibitor of glutathione synthesis, decreased the intensity of 5CMF fluorescence to 0.61. Results indicate that 5CMF fluorescence can be attenuated by agents that decrease the level of cellular nonprotein thiols, suggesting that 5CMF fluorescence is utilized for estimating the level of cellular glutathione. Hydrogen peroxide (10 μM to 3 mM) reduced the intensity of 5CMF fluorescence in a dose-dependent manner and increased the number of thymocytes stained with ethidium (presumably dead cells or cells with compromised membranes) at concentrations of 300 μM or greater. Reduction of cellular glutathione level seems to precede cell death in which oxidative stress is involved.View full abstractDownload PDF (490K) -
Tomonobu Koizumi, Yuji Saita, Akira Miyake, Akito Nishida, Hidenori Ya ...1996 Volume 71 Issue 4 Pages 307-313
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe recently isolated a cDNA clone for the human cholecystokinin (CCK)B/gastrin receptor and permanently expressed this receptor cDNA in NIH-3T3 cells. [125I]CCK-8 specifically bound to the membrane of the transfectant, and this binding was displaced by unlabeled CCK-8 with an IC50 of 0.32 nM. Treatment of these cells with CCK-8 increased the intracellular Ca2+ concentration with an EC50 of 0.30 nM. Using these cells expressing functional human CCKB/gastrin receptors, we investigated the pharmacological properties of (R)-1-[2, 3-dihydro-l-(2''-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl) urea (YM022), a potent and selective CCKB/gastrin receptor antagonist in rats. YM022 potently inhibited [125I] CCK-8 binding to the membrane with an IC50 of 55 pM and CCK-8-induced Ca2+ mobilization with that of 7.4 nM. On the other hand, its racemate and enantiomer more weakly inhibited this binding (IC50 of 110 pM and 11 nM, respectively) and Ca2+ mobilization (IC50 of 18 nM and 94 nM, respectively). These results indicate that YM022 stereoselectively recognizes the human CCKB/gastrin receptor as a potent antagonist and that the established transfectant is useful for characterization of human CCKB/gastrin-receptor ligands.View full abstractDownload PDF (467K) -
Hideki Ohnota, Tsuyoshi Kitamura, Mayumi Kinukawa, Shuichiro Hamano, N ...1996 Volume 71 Issue 4 Pages 315-323
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted by KAD-1229 on the post-prandial plasma glucose rise in STZ-induced mild NIDDM (mNIDDM) rats were different from those of sulfonylureas. When KAD-1229 with liquid meal (10 kcal/kg) was given to the mNIDDM rats, the plasma glucose migration was similar to that of normal healthy rats. On the contrary, glibenclamide had little or no effect on the plasma glucose rise 0.5—1 hr after oral administration, and its effect was only evident 2—5 hr after dosing. Tolbutamide showed similar hypoglycemia to that induced by glibenclamide at 2—5 hr with insufficient efficacy at 0.5 hr. Gliclazide sufficiently suppressed the level of post-prandial plasma glucose. However, its complete inhibition of post-prandial plasma glucose was associated with the extra-hypoglycemia 1—5 hr after oral administration. We also tested the efficacy of KAD-1229 in more severe STZ-induced NIDDM (sNIDDM) rats to elucidate the effects of the drug on the long-term glycemic controls and diabetic complications. When the sNIDDM rats were treated with 10 mg/kg KAD-1229 twice a day for about 17 weeks, increases in fasting plasma glucose and hemoglobin A1c were inhibited. Furthermore, treatment with KAD-1229 suppressed the development of microalbuminuria and cortical cataract. We conclude that the rapid- and short-acting insulinotropic agent KAD-1229 is able to improve the deterioration in the glycemic controls and inhibit the development of diabetic complications in STZ-induced NIDDM rats.View full abstractDownload PDF (628K) -
Katsuo Furukawa, Russell Chess-Williams, Toshimitsu Uchiyama1996 Volume 71 Issue 4 Pages 325-331
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe α1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit corpus cavernosum penis (CCP) was investigated using selective α1-adrenoceptor subtype antagonists. WB4101 ((2-(2, 6-dimethoxy-phenoxyethyl)-aminomethyl-l, 4-benzodioxane) hydrochloride), 5-methylurapidil and tamsulosin concentration-dependently produced a parallel rightward shift of the concentration-response curve to phenylephrine, yielding pKB values of 8.05, 7.59 and 9.21, respectively. The slopes of the Schild plots were not different from unity. These antagonists did not affect the maximum response to phenylephrine. Oxymetazoline (1 μM), which initially caused a small contraction, produced a parallel rightward shift of the concentration-response curve to phenylephrine with an apparent pKB value of 6.99. However, oxymetazoline seemed to act as a non-surmountable antagonist to the phenylephrine-induced contraction, reducing the maximum response by 71.1 %. Chloroethylclonidine (25 and 100 μM) produced a parallel rightward shift of the concentration-response curve to phenylephrine without altering the maximum response. These results show that the α1-adrenoceptor in rabbit CCP has a relatively low affinity for WB4101, 5-methylurapidil, tamsulosin and oxymetazoline and is sensitive to inactivation by chloroethylclonidine. It is suggested that the α1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit CCP has the characteristics of the α1B-adrenoceptor subtype.View full abstractDownload PDF (473K) -
Manoj Lakhe, Yasuyuki Furukawa, Takanori Yonezawa, Yoshito Nagashima, ...1996 Volume 71 Issue 4 Pages 333-335
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSWe investigated the effects of U-92032 ((7-((bis-4-fluorophenyl)methyl)-1-piperazinyl)-2-2(2-hydroxyethylamino)-4-(1-methylethyl)-2, 4, 6-cycloheptatrien-l-one), a novel T-type Ca2+ channel blocker, on sinus rate and atrial contractile force in the isolated, blood-perfused atrium of the dog. U-92032 (1 to 300 nmol) induced negative chronotropic and inotropic responses in a dose-dependent manner, and the percentage decrease in sinus rate was less than that in atrial contractile force. Atropine did not affect the negative responses to U-92032. These results suggest that U-92032, a T-type Ca2+ channel blocker, simultaneously decreases the sinus rate and atrial force as do L-type Ca2+ channel blockers in the isolated dog atrium.View full abstractDownload PDF (220K) -
Ken-ichi Furukawa, Kazuki Shibusawa, Nattaya Chairungsrilerd, Tomihisa ...1996 Volume 71 Issue 4 Pages 337-340
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSα-Mangostin, the principal ingredient of the fruit hull of Garcinia mangostana, caused a concentration-dependent decrease in the activities of both Ca2+-ATPase and Ca2+-transport of the sarcoplasmic reticulum from rabbit skeletal muscle with an IC50 value of 5 μM. Neither Ca2+ release nor other enzyme activities were affected by α-mangostin. Kinetic analysis of the inhibitory effects of α-mangostin on Ca2+-ATPase suggests that the inhibition of the ATPase is a noncompetitive-type with respect to ATP or Ca2+. α-Mangostin may become a useful pharmacological tool for clarifying the physiological functions of Ca2+-pumping ATPase and sarcoplasmic reticulum.View full abstractDownload PDF (219K) -
Masaoki Takano, Junya Kondo, Katsutoshi Yayama, Hiroshi Okamoto1996 Volume 71 Issue 4 Pages 341-343
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSExpression of the low-molecular-weight kininogen (L-kininogen) mRNA in the human fibroblast cell line WI38 was examined by means of the reverse-transcription polymerase chain reaction and Southern blotting using human L-kininogen cDNA as a probe. The results demonstrated that WI38 fibroblasts expressed L-kininogen mRNA and that the expression was stimulated by 1 mM dibutyryl cAMP or 10 μM prostaglandin E2. Dexamethasone (1 μM) inhibited the stimulatory effect of prostaglandin E2. These results suggest that human fibroblasts supply L-kininogen, a protein precursor of the inflammatory mediator kinins, to connective tissues in response to inflammatory stimuli and that glucocorticoids may exert the antiinflammatory effect in part by inhibiting the local production of L-kininogen.View full abstractDownload PDF (250K) -
Nguyen Thi Thu Huong, Kinzo Matsumoto, Kazuo Yamasaki, Nguyen Minh Duc ...1996 Volume 71 Issue 4 Pages 345-349
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSThe effect of majonoside-R2 on morphine and U-50, 488H-induced antinociception was examined by the tail-pinch test in mice and compared with that of diazepam. Majonoside-R2 and diazepam inhibited the morphine and U-50, 488H-induced antinociception, and the actions were antagonized by the benzodiazepine receptor antagonist flumazenil and the GABA-gated Cl- channel blocker picrotoxin. Diazepam but not majonoside-R2 exhibited a protective activity against convulsion caused by the GABAA antagonists bicuculline and picrotoxin. These results indicate that GABAA systems are involved in the effect of majonoside-R2 on the opioid-induced antinociception and suggest that the mechanisms of action of majonoside-R2 may differ from those of diazepam.View full abstractDownload PDF (317K) -
Kimihiro Yamashita, Yasufumi Kataoka, Mihoko N.-Nakashima, Yasuko S.-Y ...1996 Volume 71 Issue 4 Pages 351-355
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSTTC-909 is a newly developed isocarbacyclin methyl ester (TEI-9090) incorporated in lipid microspheres. The neuroprotective effect of TTC-909 was histologically examined in the pyramidal cell layer of the hippocampus CA1 subfield 7 days after transient forebrain ischemia using stroke-prone spontaneously hypertensive rats. TTC-909, given intravenously 10 min after the transient forebrain ischemia, dose-dependently protected against ischemia-related delayed neuronal death. The blood pressure remained unchanged following TTC-909 administration. This finding suggests that TTC-909 has a neuroprotective action on ischemic delayed neuronal death in the hippocampus.View full abstractDownload PDF (368K) -
Shogo Tokuyama, Fumihiro Nakamura, Kaoru Nakao, Masakatsu Takahashi, H ...1996 Volume 71 Issue 4 Pages 357-360
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSReinforcing effects of dihydroetorphine (DHE) and morphine were evaluated by the conditioned place preference paradigm. Both DHE and morphine produced an antinociceptive effect in a dose-dependent manner. On the other hand, DHE (0.1, 1, 3 and 10 μg/kg, i.p.) failed to induce the conditioned preference, while morphine (0.1, 1, 3 and 10 mg/kg, i.p.) caused a dose-dependent preference for the drug-paired place. Thus, these characteristic properties of DHE make it attractive for development as a novel potent analgesic compound that has less dependence liability.View full abstractDownload PDF (279K) -
Yasunori Ishii, Katsuhiko Muraki, Atsushi Kurihara, Yuji Imaizumi, Min ...1996 Volume 71 Issue 4 Pages 361-365
Published: 1996
Released on J-STAGE: April 06, 2006
JOURNAL FREE ACCESSEffects of sematilide, a novel class III antiarrhythmic agent, on the delayed rectifier K+ current (IK) were examined in guinea pig atrial myocytes using a voltage clamp technique. Sematilide inhibited both time-dependent outward current upon depolarization and tail currents (IK-tail) at −40 mV. The concentration of sematilide required for a 50% decrease in IK-tail was approximately 50 μM. The sematilidesensitive current obtained using a triangular voltage command exhibited marked inward rectification and had the maximum amplitude at −30 mV. These results suggest that sematilide inhibits rapidly activating IK in guinea pig atrial myocytes, resulting in the prolongation of action potential duration and refractoriness.View full abstractDownload PDF (284K)
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