Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 107, Issue 2
Displaying 1-4 of 4 articles from this issue
  • Masatoshi HAGIWARA
    1996 Volume 107 Issue 2 Pages 47-52
    Published: 1996
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Transcription of a number of eukaryotic genes is activated in response to an increase in the intracellular cAMP concentration. These genes stimulated by cAMP have a common promoter element, cAMP response element (CRE). The CRE is recognized by a CRE binding protein, CREB. The binding of CREB to CRE does not induce transcription. Activation of transcription requires the phosphorylation or CREB at Ser-133. In the case of the cAMP pathway, the activated catalytic subunit of cAMP-dependent protein kinase (PKA) translocates to the nucleus and phosphorylates Ser-133 of CREB. In the nervous system, signals transmitted across synapses are known to regulate gene expression in the post-synaptic cell. This process often involves membrane depolarization and subsequent amplification of intracellular Ca2+. The transcriptional activation induced by membrane depolarization and Ca2+ influx is mediated by a promoter element, called the Ca2+ responsive element (CaRE). Recent studies of c-fos and proenkephalin gene expression have shown that the CaRE is indistinguishable from a CRE. In this paper, we focus on the possible interactions between Ca2+ and the cAMP signaling pathways into the nucleus.
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  • Teiko TOYOGUCHI, Yoshito NAKAGAWA, Hiroshi WATANABE
    1996 Volume 107 Issue 2 Pages 53-66
    Published: 1996
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    We examined drug interactions of vancomycin hydrochloride (VCM) in the rabbit kidney. VCM has an antibacterial action against Gram positive bacteria, but composite infection patients must be jointly treated with antibiotics that are effective on Gram negative becteria, e.g., imipenem (IPM)-cilastatin sodium (CS) compounding agent. Both VCM and IPM have the adverse reaction of nephrotoxicity, whereas CS restrains the nephrotoxicity of IPM. To clarify the interactions, we examined the nephrotoxicity and pharmacokinetics of VCM in the rabbit and compared them with those in rabbits administered VCM with CS or IPM-CS. Symptoms of nephrotoxicity such as an increase of serum creatinine concentration and BUN and a morphological change of the kidney were observed with iv. injection of VCM at 300 mg/kg. However, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM plus CS or IPM-CS. Clearance and urinary excretion of VCM obviously increased in the groups injected with VCM plus CS or IPM-CS. In addition, it was estimated that VCM was actively transported by observation of the uptake in rabbit renal slices. Futhermore, the uptake rate of VCM in the renal cortex was significantly decreased by CS. Together with the above findings, it is suggested that the restraint effect of VCM uptake into nephrocytes by CS is one of the decreasing mechanisms of the nephrotoxic effect of VCM.
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  • Haruo SEKIGUCHI, Ayumi OHSAWA, Fumiyoshi KOBAYASHI, Hideo OHKUBO, Fuku ...
    1996 Volume 107 Issue 2 Pages 67-78
    Published: 1996
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investi gated grossly and histologically in comparison with that of cimetidine. The ulcer was induced b` topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer in duction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of heal ing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.
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  • Masaharu DOZEN, Kiyoshi WATANABE, Masahiro HOSONO, Yutaka HAYASHI
    1996 Volume 107 Issue 2 Pages 79-89
    Published: 1996
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Effect of cilnidipine (CIL) on renal function in SHR were evaluated in comparison with that of nifedipine (NIF) and nicardipine (NIC). In conscious SHR, CIL (3 and 10 mg/kg, p.o.) increased the urine volume, urinary Na+ excretion and urinary Na+/K+ ratio. NIF (3 and 10 mg/kg, p.o.) and NIC (10 mg/kg, p.o.) also increased the urine volume and urinary Na+ excretion, but not the urinary Na+/K+ ratio. In anesthetized SHR, CIL (3 and 10 μg/kg, i.v.) and NIF (10μg/kg, i.v.) elevated the renal blood flow (RBF), but NIC did not. CIL (10 μg / kg, i.v.) also increased the glomerular filtration rate (GFR), whereas NIF did not. Furthermore, we investigated the effect of these three drugs on endothelin (ET)-induced renal dysfunction in anesthetized SHR. ET (2μg/ kg, i.v. +30 ng/kg/min) prolongly reduced RBF, GFR and urine volume by 47, 60 and 48%, respectively. CIL (1 ?? 10 μg/kg, i.v.) improved the decrease in RBF and urine volume induced by ET as well as NIF and NIC. When blood pressure was lowered to the similar extent among the three drugs in ET-treated SHR, CIL increased the RBF and urine volume compared with the others. NIF and NIC did not affect the reduction in GFR by ET, but CIL (0.3 ?? 3 μg/kg, i.v.) significantly increased GFR. These results suggest that CIL, NIF and NIC all have natriuretic action and no suppressive action on renal function in SHR. In addition, CIL has an ameliorative effect on renal dysfunction in ET-treated SHR, suggesting that CIL might improve renal dysfunction not only in hypertensive patients but also in those with acute renal failure.
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