Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 106, Issue 6
Displaying 1-4 of 4 articles from this issue
  • Hiroshi HIGUCHI, Bing-Sheng LI
    1995Volume 106Issue 6 Pages 365-378
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Second messenger systems regulate transcription initiation of immediate-early genes (IEGs) through phosphorylation of transcriptional factors and repressors. Tissue-specific late response genes (LRGs) are induced dependently on protein synthesis slowly after IEGs, but the mechanisms of regulation of LRGs are still unknown. In this review, the mechanisms of transcriptional regulation of IEGs are summarized and possible drug action sites are discussed. As to the neuropeptide Y (NPY) gene, a typical neuronal LRG, the approach was introduced to elucidate the transcriptional regulations of the NPY gene induced by membrane depolarization and NGF-induced neuronal differentiation. The second messenger systems were Ca/calmodulin dependent protein kinases (CaM) and NGF-induced MAP kinases, respectively. The unique CaM- and NGF-responsive elements and DNA-binding factors were identified. The NDF1 protein bound to NGF-RE were cloned and characterized. NDF1 seems to a novel transcriptional factor that regulates neurotrophin-induced transcription of LRGs. Thus identification of novel regulatory factors is required to elucidate mechanisms of gene expression including transcriptional initiation, and pharmacological studies are also necessary to discover the novel drug action sites in the gene expression system.
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  • Yoshimasa WATANABE, Mayumi KAWABE-MORI, Takeo ITOH
    1995Volume 106Issue 6 Pages 379-383
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    For simultaneous measurement of [Ca2+]i and tension in intact smooth muscle and for tension measurement in skinned smooth muscle, a method for preparing a fine vascular smooth muscle strip was described. This preparation is useful for an extensive investigation of the excitation-contraction coupling mechanisms in vascular smooth muscle under physiological conditions.
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  • Masatoyo KAGOSHIMA, Hisamasa KODAIRA, Masato TANAKA, Hideyo SHIMADA
    1995Volume 106Issue 6 Pages 385-392
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    We examined the effect of FRG-8813, a new histamine H2-receptor antagonist, on 1 % NH3-induced gastric mucosal lesions and basal gastric mucus production in rats. The effect of FRG-8813 (10 mg/kg) given orally was investigated macroscopically and histochemically compared with that of 16, 16-dimethyl prostaglandin E2 (dmPGE2, 2μg/kg) or capsaicin (Cap, 10 mg/kg) in the fundic gland area. FRG-8813, dmPGE2 and capsaicin inhibited the NH3-induced mucosal lesions, and stimulated the mucus secretion 5 min after the administration. Chemical deafferentation abolished the gastroprotective effect of FRG-8813 or Cap and attenuated the increase by FRG-8813, dmPGE2 or Cap in mucus secretion seen after 5 min. These results suggest that FRG-8813 exerts its effect on gastric mucus production partially through the capsaicin-sensitive afferent nerves, like the mechanism involved in gastroprotection, and that the increase in mucus production by FRG-8813 is at least in part responsible for the gastroprotection.
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  • Kiyoshi WATANABE, Masaharu DOZEN, Yutaka HAYASHI
    1995Volume 106Issue 6 Pages 393-399
    Published: 1995
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Effect of cilnidipine, a new calcium antagonist, on autoregulation of cerebral blood flow was studied in spontaneously hypertensive rats. Cilnidipine, at doses of 1-100 μg/kg, i.v., showed a hypotensive effect in a dose-dependent manner without affecting regional cerebral blood flows (rCBF) in the cerebral cortex or nucleus caudatus. At intraduodenal doses of 1 or 10 mg/kg, cilnidipine also did not affect rCBFs, while it produced long-lasting hypotension with a slow onset, decreasing blood pressure by about 40% of the pre-administration value at 10 mg/kg. Cilnidipine at a dose of 10 mg/kg, i.d. significantly lowered the lower limit for autoregulation of cerebral blood flow. These findings suggest that autoregulation of cerebral blood flow remains intact even in the excessive hypotension induced with cilnidipine and that the drug shifts the lower limits for autoregulation of cerebral blood flow downward.
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