Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 113, Issue 3
Displaying 1-6 of 6 articles from this issue
  • Eiichi TAIRA
    1999 Volume 113 Issue 3 Pages 133-143
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Recent studies identified a novel cell adhesion molecule, gicerin, that exists on the surface of developing neurons. Determination of the amino acid sequence revealed that this molecule has five immunoglobulinlike structures in its extracellular domain and a short cytoplasmic tail. Gicerin binds in a homophilic manner and also displays heterophilic binding activity to NOF (Neurite Outgrowth Factor), which belongs to the laminin family extracellular matrix molecule. We clarified that there are two subtypes of gicerin that differ only in the cytoplasmic domain. S-gicerin, which has smaller tail, has stronger activity in cell aggregation or NOF binding. This suggests a physiological difference in the activity of each subtype. In the nervous system, gicerin is expressed during its developmental stage when neurons migrate or extend neurites to form a neural network. Gicerin promotes neurite extension from embryonic neurons by both homophilic adhesion and heterophilic adhesion to NOF. These data suggest. that gicerin participates in the formation of neural tissues. Gicerin is also expressed in other tissues such as the kidney and trachea. In these tissues, gicerin expression is also observed during the regeneration process and in tumors in addition to being present during the developmental stage. We believe that gicerin plays an important role in the histogenesis of the nervous system as well as other tissues.
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  • Shigeru KANEKO, Daisaburo NAKANO, Masahiro OHARA, Tsukao NISHIMORI
    1999 Volume 113 Issue 3 Pages 145-156
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Propiverine is a drug for the treatment of incontinence and pollakiuria. The effects of propiverine on isolated rat and dog urinary bladder were investigated. At doses of 10-6-3×10-5M, propiverine caused both a rightward shift and inhibition of the maximum response in the acetylcholine (ACh) dose-response curve. The pA2 values for rat and dog urinary bladder were 5.97 and 6.62, respectively. At doses of 10-6-10-5M, propiverine also dose-dependently inhibited KCl (100 mM)-induced contractions. The IC50 values for rat and dog urinary bladder were 3.9×10-6M and 3.8×10-6M, respectively. The pA2 value and the IC50 value of terodiline for rat urinary bladder were 6.08 and 6.6×10-6M, respectively. In contrast, the pA2 value and the IC50 value of oxybutynin for rat urinary bladder were 7.69 and 4.5×10-6M, respectively, suggesting that oxybutynin exerts an anti-muscarinic effect at doses at which no discernible anti-KCl effect was observed, whereas propiverine and terodiline exerted both effects at the same doses. The inhibitory effect of drugs on the contraction induced by electrical field stimulation was tested. At a dose of 10-7g/ml, tetrodotoxin inhibited the contraction of rat and dog urinary bladder by 76.6% and 92.6%, respectively. Propiverine and verapamil dose-dependently inhibited the contractile response induced by electrical field stimulation at doses of 10-5M or more and 3×10-6M or more, respectively. At these concentrations, a marked anti-KCl effect of the drugs on smooth muscle was observed. On the other hand, atropine caused no inhibition of the contractile response in rat urinary bladder at a dose of 3×10-5M, and it inhibited the contraction in dog urinary bladder by 14.9% at a dose of 10-5M. These findings suggest that although propiverine exhibits both anti-muscarinic and anti-KCl effects in isolated rat and dog urinary bladder, the inhibitory effects of propiverine on the atropine-resistant part of contraction may be mainly due to its anti-KCl effect.
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  • Mitsuhiro NAGAO, Shigeru KANEKO, Tomio HIROTA, Mitsutaka ISOGAI, Hitos ...
    1999 Volume 113 Issue 3 Pages 157-166
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Propiverine is a drug for the treatment of incontinence and pollakiuria. Such micturitional disorders are principally caused by a hyperactive bladder. The effects of propiverine, its active metabolite, 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4 (N→O)), oxybutynin and terodiline on muscarinic receptors in guinea pig urinary bladder, salivary glands, cerebral cortex, ileal longitudinal muscle and heart were compared. Both propiverine and DPr-P-4 (N→O) competitively inhibited specific binding of 3H-quinuclidinyl benzilate (3H-QNB) to membrane fractions of these tissues. Oxybutynin, terodiline, pirenzepine and atropine also competitively inhibited the binding of 3H-QNB. The order of these drugs in terms of their affinity for muscarinic receptors was as follows: atropine > oxybutynin > pirenzepine, DPr-P-4 (N→O), terodiline > propiverine. Propiverine and DPr-P-4 (N→O) had no selectivity for muscarinic receptors in these tissues, the same as atropine. In contrast, pirenzepine, a Ml-selective drug, had 10.1 times greater affinity for muscarinic receptors in the cerebral cortex than in urinary bladder, and the affinity of oxybutynin for muscarinic receptors in salivary glands and in cerebral cortex was 10.9 times and 13.9 times higher, respectively, than in urinary bladder. The affinity of terodiline for muscarinic receptors in the cerebral cortex was 4.4 times higher than in urinary bladder. In this study, the effect of propiverine and oxybutynin on pilocarpine (1 mg/kg, s.c.)-induced salivation in conscious dogs was also compared. Propiverine (5 mg/kg, i.v.) had no effect on pilocarpine-induced salivation, whereas oxybutynin (0.1 mg 0.5 mg/kg, i.v.) inhibited it significantly and dose-dependently. The ID50 values (95% confidence limits) for propiverine and oxybutynin during the 20 min after intravenous administration were 6.88 mg/kg (4.71-15.67) and 0.154 mg, /kg (0.115-0.205), respectively. These findings suggest that although propiverine, its active metabolite DPr-P-4 (N→O), oxybutynin and terodiline competitively inhibit the binding of 3H-QNB to muscarinic receptors, the affinity of these drugs for the muscarinic receptors of these tissues is very different and that propiverine has less effect on salivation than oxybutynin.
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  • Yasuko DOI, Yukio MORI, Noriko URATA, Midori MIZUO, Mihoko SYOJI, Shig ...
    1999 Volume 113 Issue 3 Pages 167-176
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    The effect of T-593, a novel anti-ulcer agent, on the healing of cryocautery-induced rat gastric ulcer was investigated histologically in comparison with that of famotidine. Seven days after ulceration, T-593 (30 mg/ kg) or famotidine (30 mg/kg) was orally administered twice daily for 8 weeks. Two, 4 and 8 weeks after the start of administration, the ulcer size was measured by a stereoscopic microscope, and the gastric mucosa was observed histologically. The thickness of the regenerated mucosa, the density and the arrangement of gastric glands, the degree of inflammatory-cell infiltration in the submucosal tissue and the number of microvessels in the submucosal tissue were quantified. In macroscopical evaluation, T-593 and famotidine significantly accelerated ulcer healing, and the time courses of the ulcer index were similar in both cases. In histological evaluation of healed ulcers, T-593 normalized the thickness of regenerated mucosa and reduced the degree of inflammatory-cell infiltration and the number of microvessels in the submucosal tissue, while famotidine had no effect. In conclusion, T-593 possesses accelerating effects not only on the restoration of regenerated mucosa but also on the maturation of submucosal tissue. Therefore, T-593 improves the quality of ulcer healing.
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  • Nobuhisa UEDA, Yuriko MAEKAWA, Hisaya OHTANI, Hiroyuki UCHIYAMA, Sanae ...
    1999 Volume 113 Issue 3 Pages 177-184
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    TO-193 (TachoComb®) is a new fibrin adhesive agent that consists of a collagen sheet coated with fibrin glue. We compared the hemostatic effect of TO-193 in several experimental models with Beriplast® P as a fibrin adhesive agent, Avitene® and Novacol® as a microfibrillar collagen hemostat, and a sponge-like collagen sheet as the constitutional parts of TO-193. In the in vitro bleeding model in which blood leaks out through cotton cloth, the pressure of TO-193 when blood leakage was observed was higher than those of Beriplast® P, Avitene®, Novacol® and the collagen sheet, indicating that TO-193 possessed a strong adhesive effect on the bleeding surface. On the kidney resection surface, TO-193 showed a more potent adhesive effect than those of Beriplast® P and the collagen sheet, suggesting that TO-193 has a potent hemostatic effect. In the liver resection, TO-193 significantly reduced the bleeding volume compared with that of Novacol® in normal rats. Furthermore, the bleeding volume of TO-193 was about half that of Beriplast® P and equivalent to that of Novacol® even in anticoagulant-treated rats. From these data, it is expected that TO-193 would be a valuable hemostatic agent for clinical use since TO-193 possesses a potent adhesive ability on the bleeding resection surface and would certainly stop bleeding in both patients with normal coagulation and those with a low blood coagulation condition.
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  • Kuniko HARA, Yasuhiro AKIYAMA, Takashi TOMIUGA, Masatoshi KOBAYASHI, H ...
    1999 Volume 113 Issue 3 Pages 185-192
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Vitamin K2 (K2), a therapeutic agent against osteoporosis, is prohibited for patients with thrombosis who are receiving warfarin (WT). However, because some aged patients with thrombosis have osteoporosis, some patients treated with WF may be administered K2 concomitantly. We investigated here the interaction between K2 and WF on thrombosis in a rat aorta loop model. Administration of WF at 0.58, 0.82 and 1.16 mg/ l in drinking water for 7 days decreased the thrombotic rate and increased the death rate, dosedependently. Therefore in the following study, 0.80 mg/l of WF was used. After 2 days of WF-treatment, 1.5, 14 and 145 mg/kg of K2 was administered for 5 days. The blood coagulation time was markedly prolonged by WF treatment for 7 days and this effect was completely inhibited by all doses of K2. WF treatment significantly decreased the cumulative thrombotic rate for 5 days. Administration of 1.5 and 14 mg/kg of K2 did not influence the WF effect on thrombosis. The thrombotic rate in the 145 mg, /kg K2 group was lower than that in the WF-control group, but similar to that in the WF-untreated group. These findings suggest that high dose of K2 reduces the effect of WF on thrombosis but does not enhance the occurrence of thrombosis more than that without WF treatment.
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