The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 73, Issue 1
Displaying 1-12 of 12 articles from this issue
  • Issei Takayanagi, Katsuo Koike, Mitsutoshi Satoh, Ayako Okayasu
    1997 Volume 73 Issue 1 Pages 1-22
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    Both α1-adrenoceptors and M3-cholinoceptors can be divided into two subtypes discriminated by the β-chloroethylamines, chloroethylclonidine and propylbenzilylcholine mustard (PrBCM), only in the presence of GTP. The full agonists interact with both subtypes to induce responses. The partial agonists activate one of them to induce responses but behave as competitive antagonists when they interact with the other. The responses mediated through the receptors that are activated by the partial agonists are resistant to myosin light chain kinase inhibitors, while the response through the activation of the other receptors are suppressed by the inhibitors. The receptor stimulations through α1A-adrenoceptor and PrBCM-sensitive M3-cholinoceptor subtypes mainly activate the myosin light chain-phosphorylationindependent pathway mediated through protein kinase C and low molecular weight GTP-binding protein, whereas the stimulations through α1B-adrenoceptors and the PrBCM-phosphorylation-dependent pathway are directly related to Ca2+ calmodulin.
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  • Kiyoko Nakamura, Mitsumasa Ohyanagi, Tadaaki Iwasaki
    1997 Volume 73 Issue 1 Pages 23-28
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    To explore alterations in messenger RNA (mRNA)for the β-adrenoceptor (β3-AR)in ischemic myocardium, we compared the mRNA levels for, β-AR in ischemic and nonischemic myocardium by in situ hybridization using a radioisotope imaging system. We also compared these mRNA levels in ischemic and nonischemic myocardium with the number of the β-AR by radioligand binding assay. The mRNAs for β-AR were diffusely distributed in normal hearts. The level of mRNA detected by in situ hybridization was reduced by acute ischemia, whereas the number of β-AR was increased. Although the number of β-AR was increased in the myocardium with one or three hours ischemia, the total function in β-AR-stimulatory G protein-adenylate cyclase system was not changed. There is a discrepancy between β-AR mRNA and protein levels in the acute ischemic rat ventricular myocardium.
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  • Katsuhisa Ikeda, Masayuki Furukawa, Noriko Tanno, Mutsuo Yamaya, Tomon ...
    1997 Volume 73 Issue 1 Pages 29-32
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    Sai-rei-to, a type of Kampo medicine (Japanese herbal medicine), has been shown to be clinically effective in treating patients with otitis media with effusion. The effect of Sai-rei-to on the ion transport of the middle ear surface epithelium cultured from the Mongolian gerbil was investigated by using an Ussing chamber. Application of Sai-rei-to to the mucosal bath but not the serosal bath induced an increase in the short-circuit current (Isc)in the basal state. The increase in Isc was almost completely inhibited by addition of diphenylamine-2-carboxylic acid but not by amiloride, indicating enhancement of Cl- secretion. On the basis of the lack of changes in the intracellular Ca2+ concentration and a sideness of action, the effect of Sai-rei-to on Isc is thought to be a direct and selective activation on the apical Cl- channel.
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  • Takatsugu Yamamoto, Li-man Wang, Kazuro Shimakura, Masaki Sanaka, Yuic ...
    1997 Volume 73 Issue 1 Pages 33-40
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    We conducted the present study to propose a rabbit model of pulmonary edema (PE)induced by angiotensin II (All)and to test the preventive effect of losartan on this form of PE. All was administered to rabbits intravenously at 50, 100, 150 or 300 μg/kg, either by continuous infusion (10 min)or by bolus injection (30 sec). Continuously administered All (150 μg/kg)induced PE in most cases, while a bolus injection of the same dosage did not. Additionally, the incidence of PE increased with higher dosages of All when it was infused continuously. A newly established parameter, the area under the systolic blood pressure-time curve corrected by baseline (cAUC), was prone to rise as the incidence of PE increased. Moreover, cAUC signficantly correlated with the wet-dry lung weight ratio (r=0.66, P<0.05). Subsequently, 0.5 or 3.0 mg/kg of losartan was given before continuous infusion of 150 μg/kg of All. The higher dosage of losartan prevented PE completely, while the lower one did so moderately. We concluded that intravenous administration of All induces PE, probably as a result of increasing afterload. Furthermore, an adequate dosage of losartan can prevent PE because it reduces the pressor effect of All.
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  • Makoto Kashiwa, Yoichi Masuyama, Hiromi Miyauchi, Taisuke Uchida, Shin ...
    1997 Volume 73 Issue 1 Pages 41-50
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    YM17E (1, 3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]benzene dihydrochloride)was found to be a potent inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT)in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-highdensity lipoprotein (HDL)fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.
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  • Atsumi Nitta, Taneo Fukuta, Takaaki Hasegawa, Toshitaka Nabeshima
    1997 Volume 73 Issue 1 Pages 51-57
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    To investigate the toxicity of β-amyloid protein, a component of the senile plaques in Alzheimer''s disease, it was infused into the cerebral ventricle of rats for 14 days by a mini-osmotic pump. Performances in the water maze and passive avoidance tasks in β-amyloid protein-treated rats were impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after the cessation of the infusion. However, the learning impairment was recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after the cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Furthermore, β-amyloid protein altered the staining in the nuclei of hippocampal cells for only 2 weeks after the cessation. These results suggest that β-amyloid protein produces some damage in the central nervous system in vivo.
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  • Hiroshi Satoh, Akio Shino, Fumihiko Sato, Shoichi Asano, Izumi Murakam ...
    1997 Volume 73 Issue 1 Pages 59-71
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF)in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580)and a monoclonal antibody for bFGF (MAb 3H3)on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.)inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001 -0.1 mg/kg × 2/day, p.o.)increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580)may be involved in its effect on ulcer healing.
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  • Kazumi Hayashi, Tadashi Nagamatsu, Tatsuya Oka, Yoshio Suzuki
    1997 Volume 73 Issue 1 Pages 73-82
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    The antinephritic effects of ONO-1301 ([7, 8-dihydro-5-[(E)-[[a-(3-pyridyl)benzylidene]aminooxy]ethyl] -1-naphtyloxy]acetic acid)on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats were investigated. ONO-1301 was orally given to crescentic-type anti-GBM nephritic rats for 40 days after the induction of nephritis. ONO-1301 (30 mg/kg) suppressed the elevation of protein excretion into urine. In the ONO-1301-treated rats, cholesterol and urea nitrogen content in the plasma was lower than that of the nephritic control rats. Histological observation demonstrated that ONO-1301 suppressed the incidence of crescent formation and adhesion of capillary wall to Bowman''s capsule. However, ONO-1301 failed to inhibit the antibody production against rabbit IgG and the rat-IgG deposition on the GBM. The increase in very late antigen-4 (CD49b, VLA-4) -positive cells in nephritic glomeruli was significantly reduced by ONO-1301 treatment on day 5. cAMP-elevating agents inhibited the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression on the surface of human umbilical vein endothelial cells (HUVECs) mediated by tumor necrosis factor (TNF) -α. These findings suggest that the antinephritic action of ONO-1301 is due to, at least in part, inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of VCAM-1.
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  • Norikazu Yamaguchi, Kazuko Fujimoto, Takeshi Fujii, Takeshi Suzuki, Ko ...
    1997 Volume 73 Issue 1 Pages 83-91
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    YM358 (2, 7-diethyl-5-[[2''-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1, 5-b] [1, 2, 4]triazole potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated by using radiotelemetry. A clear diurnal variation in blood pressure, heart rate and locomotor activity was observed in synchrony with the light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood pressure in a dose-dependent manner. Although a mild attenuation of the antihypertensive effect of YM358 was observed during the early stage of therapy, YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr MAP and DAP, and it prevented the further development of hypertension. YM358 did not affect either heart rate or locomotor activity or their diurnal variations. After the discontinuation of therapy with YM358, the blood pressure recovered promptly to the control level while there was no sign of a rebound increase in blood pressure. These results suggest that YM358 may be potentially useful for the treatment of hypertension.
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  • Mikiko Okada, Naoyuki Hayashi, Motohiko Kometani, Kenzo Nakao, Toshiya ...
    1997 Volume 73 Issue 1 Pages 93-96
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    The effect of ovariectomy and continuous subcutaneous replacement of 17β-estradiol was examined in female Wistar rats. Tail skin temperature significantly increased in ovariectomized rats 6 days after ovariectomy, and the elevated level was sustained until 21 days after ovariectomy. 17β-Estradiol at doses of 0.3 and 1.0 μg/body/day suppressed the increases in tail skin temperature. In the forced swimming test, the ovariectomized control rats showed significantly prolonged immobility time in comparison with sham-ovariectomized rats 14 days after ovariectomy. The duration of immobility of ovariectomized rats treated with 17β-estradiol (0.3, 1.0, 3.0 μg/body/day)or maprotiline (0.6 mg/body/day)was significantly shorter than that of ovariectomized control rats.
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  • Mei-Yu Geng, Hiroshi Saito, Nobuyoshi Nishiyama
    1997 Volume 73 Issue 1 Pages 97-100
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    When hippocampal cultures were deprived of glucose, massive release of lactate dehydrogenase (LDH), an indicator of neuronal death, occurred 24 hr following the onset of hypoglycemic insult via N-methyl-D-aspartate (NMDA)-type glutamate receptor activation. Ifenprodil (0.1 and 1 M)significantly inhibited LDH release, which was antagonized by polyamines. These results suggest that ifenprodil protects neurons from glucose deprivation by antagonizing the effects of glutamate via selective interaction with polyamine modulatory sites on the NMDA receptor complex. The observed phenomenon further indicate that ifenprodil might be used prophylactically against neuronal death induced by excitotoxic disorders.
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  • Susumu Shiraishi, Tomio Okamura, Noboru Toda
    1997 Volume 73 Issue 1 Pages 101-103
    Published: January 01, 1997
    Released on J-STAGE: April 06, 2006
    JOURNAL FREE ACCESS
    Dog hepatic arterial strips treated with prazosin responded to norepinephrine with concentration-related, endothelium-independent relaxations, the maximal response being 81.7% of the papaverineinduced maximal relaxation that was markedly greater than that in renal arteries. The norepinephrineinduced relaxation in hepatic arteries was significantly attenuated by metoprolol but not influenced by butoxamine. Relaxant responses to norepinephrine of dog hepatic arteries appear to be mediated by the β1-adrenoceptor subtype, like those of coronary arteries. Evidence for functioning of the β1-subtype in hepatic arteries would contribute to the analysis of neural and hormonal regulation of blood flow in the liver.
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