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Masakatsu Takahashi, Hiroshi Kaneto
1991 Volume 56 Issue 2 Pages
121-126
Published: 1991
Released on J-STAGE: July 11, 2006
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The site of action involved in the suppression by exposure to footshock (FS)- and psychological (PSY)-stress of the development of antinociceptive tolerance to morphine has been investigated. Daily treatment with 10 mg/kg, s.c.; 3μg, i.t.; and 5μg, i.c.v. of morphine, regardless of the administration route, resulted in the development of tolerance. Daily exposure to FS- or PSY-stress suppressed the development of tolerance to s.c. and i.t. administered morphine but not that to i.c.v. administered morphine. Pretreatment with 2 mg/kg, i.p. of nor-binaltorphimine (nor-BNI) abolished the suppressive effect of PSY-stress on the development of tolerance to morphine given s.c. The suppression by PSY-stress was also antagonized by 2μg, i.t. of nor-BNI and not by 2μg, i.c.v. of nor-BNI. Thus, the development of tolerance in the spinal cord due to interaction of morphine at μ-opioid receptors can be suppressed by exposure to these stresses, probably through the descending signals from the supraspinal area, and activation of κ-opioid receptors in the spinal cord could also participate in the suppression by PSY-stress.
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Mitsuhiko Yamada, Yuji Kiuchi, Miyuki Hashimoto, Katsuji Oguchi, Hajim ...
1991 Volume 56 Issue 2 Pages
127-132
Published: 1991
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Reverse tolerance to stereotyped behavior was induced after repeated administration of β-phenylethylamine (PEA) (50 mg/kg, i.p., daily for 10 days) in rats. The reverse tolerance was maintained for at least 4 weeks after the last administration. We studied the effects of acoustic stimulation on locomotor activity 2 days and 4 weeks after withdrawal from PEA and measured the changes in brain monoamine levels 4 weeks after the withdrawal. Locomotor activity during acoustic stimulation was increased in the saline treated group, and this response was unaffected after repeated PEA treatment. Four weeks after withdrawal, significant increases in noradrenaline levels in the cerebral cortex and decreases in 5-hydroxytryptamine levels in the hypothalamus were found. The effects of acoustic stimulation on locomotor activity and the changes in brain monoamine levels were different from those of methamphetamine treatment obtained in our previous study. In conclusion, it may be suggested that the response to acoustic stimulation after repeated PEA administration in rats cannot be a model for abnormal responsiveness to environmental stimulation that is observed in chronic paranoid schizophrenics.
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Yasusuke Masuda, Yasuko Yamamori
1991 Volume 56 Issue 2 Pages
133-142
Published: 1991
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Lipid peroxidation was assessed histologically and biochemically in hemoglobin-free perfused rat livers using two different types of stimulators. The Schiff reaction of fuchsin with cellular aldehydes was used as a histological index for lipid peroxidation.
t-Butyl hydroperoxide (BHP, 0.8 mM) infusion caused a rapid and sustained release of thiobarbituric acid reactive substances (TBARS) into the effluent perfusate for up to 60 min, which was accompanied by lactate dehydrogenase (LDH) leakage after 30 min. The Schiff positive foci were initially restricted to periportal zones and spread with time to whole areas, accompanied by periportal necrosis. Co-infusion of diphenyl-p-phenylenediamine suppressed the TBARS release, with negative fuchsin staining, but the LDH leakage was unaffected. Under retrograde perfusion, BHP produced pericentral staining and necrosis. With 2.5 mM ADP-100μM Fe
3+, little TBARS was released up to 60 min, even though the hepatic TBARS levels increased considerably by this time. By 90 min, marked TBARS release occurred, but LDH leakage remained low. Irrespective of the direction of perfusion, pericentral hepatocytes became Schiff positive after 30 min. The fuchsin staining method may be useful for detecting peroxidized zones of the liver lobules.
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Yasusuke Masuda, Yasuko Yamamori
1991 Volume 56 Issue 2 Pages
143-150
Published: 1991
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Bromotrichloromethane (CBrCl
3)-induced hepatic lipid peroxidation and cell necrosis were studied histologically and biochemically, using isolated perfused livers from phenobarbital-pretreated rats. Lipid peroxidation was assessed by fuchsin staining of the liver slices and release of thiobarbituric acid reactive substances (TBARS) into the perfusate; necrosis was assessed by trypan blue uptake and lactate dehydrogenase (LDH) leakage. A good correlation was observed between the Schiffpositive reaction and TBARS release under various experimental conditions, supporting the validity of the fuchsin staining method for histological detection of lipid peroxidation. Lobular localization of lipid peroxidation and necrosis was as follows: Under high oxygen supply (95% O
2-saturated buffer), infusion of CBrCl
3 caused the Schiffpositive reaction in the pericentral to midzonal hepatocytes, irrespective of the direction of perfusion, but did not produce necrosis. Under low oxygen supply (20% O
2) with retrograde perfusion, dissociation of lipid peroxidation and necrosis was observed, i.e., trypan blue uptake in the periportal zones and Schiff-positive staining in the pericentral hepatocytes. Thus, lipid peroxidation by itself may have a relatively minor role in the development of CBrCl
3-induced acute hepatic cell death.
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Issei Takayanagi, Hiroshi Ohtsuki, Kiyoshige Saito, Katsuo Koike, Mits ...
1991 Volume 56 Issue 2 Pages
151-158
Published: 1991
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Pilocarpine, a partial agonist, activates propylbenzilylcholine mustard (PrBCM)-sensitive cholinoceptors in the guinea pig ileal longitudinal muscle, while carbachol, a full agonist, predominantly activates PrBCM-resistant ones. Carbachol behaves as a partial agonist in the preparation treated with phenoxybenzamine and mainly activates PrBCM-sensitive cholinoceptors, as phenoxybenzamine preferably blocks PrBCM-resistant ones. The receptor occupancy-response curve for carbachol became a rectangular hyperbola, while pilocarpine showed a linear relation. After occlusion of cholinoceptors with phenoxybenzamine, carbachol showed a linear receptor occupancy-response relation, suggesting that its contraction mechanisms after occlusion of cholinoceptors resemble those for pilocarpine. Both the agonists induced an increase in cytosolic Ca
2+ concentration ([Ca
2+]
i) and tension development in a concentration-dependent manner under the conditions used herein. The slopes of the regression lines between [Ca
2+]
i and tension development for pilocarpine in the untreated preparation and for carbachol in the preparation treated with phenoxybenzamine were significantly steeper than that for carbachol in the untreated preparation, suggesting that carbachol in the phenoxybenzamine-treated preparation and pilocarpine induced a greater tension for a given increase in low [Ca
2+]
i than did carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca
2+-sensitivity of the contractile elements.
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Takao Saeki, Issei Ohtsuka, Ryoichi Hashida, Hiroyuki Shiojiri, Isao Y ...
1991 Volume 56 Issue 2 Pages
159-166
Published: 1991
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The development of atheromatous lesions in the aortic arch of 0.5% cholesterol-fed rabbits was biochemically and morphologically examined. The animals were killed at week twelve (Cont-12W) or sixteen (Cont-16W). Both the micrographic and biochemical studies showed that the main atheromatous lesions in the Cont-12W group were fatty streaks, whereas those in the Cont-16W group were fibrous plaques. In these models, oral ingestion of 0.2% and 0.4% E5050, which has an antiproliferative effect on smooth muscle cells, had no effect on the surface involvement or the lipid content of the aortic arch at the sixteenth week, but reduced the degree of intimal thickening and the DNA content in the aortic arch in a dose-dependent manner. These results strongly suggest that E5050 suppresses the intimal thickening through its inhibitory effect on the proliferation of smooth muscle cells.
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Yumiko Ushio, Hiroko Abe
1991 Volume 56 Issue 2 Pages
167-175
Published: 1991
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The effects of saikosaponin-d (ssd), isolated from
Bupleurum radix, on phagocytic functions of mouse peritoneal macrophages were investigated in macrophage cultures after treatment in vivo. We also compared the ultrastructural appearances of macrophages from ssd-treated mice with those from control mice. The macrophages from ssd-treated mice showed a significant increase in phagocytosis, intracellular killing of yeast and acid phosphatase activity. Treatment of mice with ssd also induced the Fc receptor expression in macrophages. The macrophages from ssd-treated mice showed more intense spreading on a glass surface than those from the control mice after a 60 min-incubation. Furthermore, the macrophages from ssd-treated mice seemed to possess a well-developed Golgi apparatus and the large vacuoles. The data suggest that the functional changes in the macrophages from ssd-treated mice are brought about by a modification in the surface membrane and the intracellular distribution.
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Akifumi Togari, Michitsugu Arai, Masatoshi Hironaka, Shosei Matsumoto, ...
1991 Volume 56 Issue 2 Pages
177-185
Published: 1991
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The present study was undertaken to test whether long term administration of HEBP could prevent the progress of bone loss induced by ovariectomy in rats. Administration of HEBP was started from day 111 after ovariectomy. The animals received subcutaneous injections of HEBP, at a dose of 0, 2, 4, or 8 mg/kg, every other day for 92 days. Tibiae, femora and incisor teeth were investigated by chemical analyses and by contact microradiography. Effects on calcium, phosphorus, and alkaline phosphatase activity in the plasma were also examined. Progress in the loss of bone density and ash content caused by ovariectomy was prevented by the administration of 2 mg/kg HEBP for 92 days and was partially prevented by the administration of 4 mg/kg. At a dose of 8 mg/kg, however, HEBP did not prevent the bone loss but, rather, potentiated it. These chemical findings were qualitatively confirmed by contact microradiography. A dose-dependent inhibition was observed in the mineralization of incisor dentin. These results suggest that HEBP, at least at low dose levels in which the inhibition of mineralization is not predominant, has a potency to prevent the progress of bone loss induced by ovariectomy. At higher doses, however, this compound seems not to be effective, because of the severe inhibition of mineralization.
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Kimiaki Saegusa, Yasuyuki Furukawa, Kunio Akahane, Masayuki Haniuda, S ...
1991 Volume 56 Issue 2 Pages
187-193
Published: 1991
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The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300μg) injected into the sinus node artery of the isolated atrium produced dose-related negative chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or norepinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve terminals and on muscarinic receptors at the effector cells in the dog heart.
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Hitoshi Ito, Hiroko Ito, Hideomi Amano, Hiroyuki Noda
1991 Volume 56 Issue 2 Pages
195-202
Published: 1991
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The antimetastatic effect of cepharanthin with or without 5-fluorouracil (5-FU) was examined in an experimental model of lung metastasis induced by Lewis lung carcinoma (3LL) in C57BL/6crSlc mice. Injection of cepharanthin i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination therapy with cepharanthin plus 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with cepharanthin. Cepharanthin depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of cepharanthin. A possible mechanism of the inhibition of lung metastases by treatment with cepharanthin may be that this drug acts through macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that combination therapy with cepharanthin plus 5-FU may have clinical value in the prevention of cancer metastasis.
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Teruo Nakadate, Satoshi Yamamoto, Yoshitaka Kamegaya, Motoko Ishihara, ...
1991 Volume 56 Issue 2 Pages
203-211
Published: 1991
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Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more prominent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-O-retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1, 2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol-13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down-regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols.
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Tadashi Kusama, Yoshie Murakoshi, Hajime Murakami
1991 Volume 56 Issue 2 Pages
213-216
Published: 1991
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An acutely acquired dependence was investigated in rat hippocampal slices after brief exposure to morphine. Morphine augmented the population spike amplitude. Naloxone not only reversed the augmentation but decreased the amplitude to a level below that of the control. The inhibitory effect of naloxone correlated with the period of preincubation with morphine. These results suggested that the decreased response may indicate the withdrawal state acquired in vitro.
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Kazuaki Hiki, Yoshiki Yui, Ryuichi Hattori, Hiroshi Eizawa, Kunihiko K ...
1991 Volume 56 Issue 2 Pages
217-220
Published: 1991
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Cytotoxic activated macrophages were sonicated and centrifuged. The activity of nitric oxide (NO) synthase was present in the supernatant and independent of Ca
2+. The pellets were washed three times and treated with buffer containing 0.1% Triton X-100 or buffer alone, followed by centrifugation. The supernatant containing Triton X-100 showed NO synthase activity that was dependent on Ca
2+, whereas the supernatant without the detergent had little activity. These data suggest that there are two forms of NO synthase: cytosolic and membrane-bound enzymes.
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Masaaki Ishikawa, Yoshio Takayanagi, Ken-ichi Sasaki
1991 Volume 56 Issue 2 Pages
221-224
Published: 1991
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We examined whether chlorpromazine (CPZ) modulates the lethality of doxorubicin (DOX, 12 mg/kg, i.p.) in mice treated with CPZ (6 mg/kg, i.p.) 1 hr before administration of DOX. Pretreatment with CPZ produced: 1) earlier deaths and 2) an increase in the number of deaths, compared to the controls. Potentiation of the bone marrow toxicity of DOX by CPZ was also reflected in the drug lethality towards the animals.
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Ryota Yoshimoto, Hideki Dohmoto, Kaoru Yamada, Atsuo Goto
1991 Volume 56 Issue 2 Pages
225-229
Published: 1991
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We examined the effects of FRC-8653, a novel dihydropyridine calcium antagonist, on the contraction of an arterial preparation and the calcium influx into vascular smooth muscle cells to clarify the long-lasting hypotensive activity of this drug. Inhibition by FRC-8653 persisted for more than 7 hr after its removal, whereas nifedipine and nicardipine exhibited shorter durations of suppressive activity. These results suggest that prolonged inhibition of calcium influx through L-channels contributes to the long-lasting vasodilative and antihypertensive activity of FRC-8653.
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Yoshihisa Kitamura, Toshio Ohnuki, Yasuyuki Nomura
1991 Volume 56 Issue 2 Pages
231-235
Published: 1991
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Senescence-accelerated mouse (SAM-P/8) is known as a murine model of aging and memory dysfunction, compared with control mouse (SAM-R/1). In the hippocampus of 9-month-old SAM-P/8, the B
max of [
3H]QNB binding was decreased compared with that of SAM-R/1 at the same age. Single and repeated administrations of bifemelane to SAM-P/8 induced an increase in the B
max of [
3H]QNB binding in the hippocampus. From these results, bifemelane seems to exert pharmacological effects through possible activation of the cholinergic system in the hippocampus of SAM.
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Akio Fujimura, Hiroyuki Kajiyama, Tsuyoshi Shiga, Kyo-ichi Ohashi, Aki ...
1991 Volume 56 Issue 2 Pages
237-240
Published: 1991
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We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration.
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Takeshi Naitoh, Shinjiro Kobayashi, Ikuko Kimura, Masayasu Kimura
1991 Volume 56 Issue 2 Pages
241-244
Published: 1991
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We investigated whether the changed levels of intracellular Ca
2+ and Mg
2+ in mouse skeletal muscles affected insulin-stimulated glucose uptake. Insulin alone had no effect on
45Ca
2+ efflux and uptake. A23187 at 20 μM increased
45Ca
2+ influx and inhibited insulin-stimulated
14C-glucose uptake with normal external concentrations of Ca
2+ and Mg
2+ or in the absence of both cations. These results suggest that the increase in Ca
2+ influx into, and in Mg
2+ efflux from, skeletal muscles may inhibit insulin-stimulated glucose uptake.
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Kazuo Aisaka, Aki Mitani, Yasuo Kitajima, Tomochika Ohno, Takafumi Ish ...
1991 Volume 56 Issue 2 Pages
245-248
Published: 1991
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N
G-Monomethyl L-arginine (L-NMMA; 0.1-10 mg/kg, i.v.), a selective inhibitor of nitric oxide (NO) synthesis derived from L-arginine, elicited a greater increase in blood pressure in urethane/α-chloralose- and pentobarbital-anesthetized rats than in conscious Wistar rats. The pressor response to phenylephrine was almost equivalent in both conscious and anesthetized rats. These findings suggest that the experimental conditions (anesthetized or conscious) modify the spontaneously released NO's contribution to blood pressure regulation in vivo.
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