Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 113, Issue 6
Displaying 1-4 of 4 articles from this issue
  • Hisashi OHTA, Tooru SATOMI, Jun SUZUKI, Fumihiko IKEMOTO, Masaru NISHI ...
    1999 Volume 113 Issue 6 Pages 331-338
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Losartan is the first orally active angiotensin II receptor type 1 antagonist for a new class of cardiovascular therapeutic agent. Losartan is converted to an active metabolite (E3174) after oral administration in humans and rats. Both losartan and E3174 contribute to the net angiotensin II receptor blockade and produce anti-hypertensive effect. Losartan not only blocks the vasoconstractive effect of angiotensin II but also inhibits its mitogenic effect; thus losartan is expected to protect against end-organ-damage-related hyper-tension and chronic heart failure. Unlike angiotensin-coverting-enzyme inhibitor, losartan does not elicit adverse effects of cough and angioneurotic edema by its blockade of angiotensin II receptor. It is also expected to reduce proteinuria in nephropathy. In addtion to its blockade of angiotensin II receptor, losartan blocks thromboxane A2 receptor and facilitates excretion of uric acid, although therapeutic importance of these effects are under investigation. In summary, losartan, an angiotensin II type 1 receptor antagonist is a new class of antihypertensive agent and its therapeutic potentials are not merely reduction of blood pressure but total protection from end-organ damage resulting from activation of both the systemic and local renin-angiotensin system.
    Download PDF (7989K)
  • Norio AKAIKE
    1999 Volume 113 Issue 6 Pages 339-347
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Cl- is one of the major ionic constituents of cells and extracellular spaces. Intracellular Cl- plays an important role in regulating the cell volume and pH, in both salt secretion and reabsorption, in membrane excitability, and G-protein-dependent intracellular signal transduction. GABA and glycine are the primary inhibitory neurotransmitters. Such agonist-stimulated responses are affected by the intracellular Cl- concentration ([Cl-]i). However, it was difficult to make an electrical recording of the physiological Cl- response from cells with native intracellular Cl- activity because of the limitations of present recording techniques using conventional glass-microelectrode, whole-cell patch and nystatin perforated patch recording modes. Recently, this difficulty was overcome by developing the gramicidin perforated patch recording mode in our laboratory. Gramicidin is a polypeptide antibiotic that forms pores in the cell membrane as well as nystatin but allows only monovalent cations to permeate the membrane, enabling both [Cl-]i and the second messenger system to remain undisturbed. Here, I would like to primarily focus on the GABA- and glycine-induced Cl- responses to in mammalian CNS neurons maintaining native cellular [Cl-]i under normal and pathological neuronal conditions by use of gramicidin perforated patch recording configuration. Age-related and developmental changes in neuronal [Cl-]i are also described in detail.
    Download PDF (7861K)
  • Hiroshi SAKAGAMI, Kazue SATOH
    1999 Volume 113 Issue 6 Pages 349-356
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Vitamin C (sodium ascorbate), gallic acid and dopamine induced apoptosis (characterized by internucleosomal DNA cleavage, nuclear fragmentation, chromatin condensation near nuclear membrane and loss of cell surface microvilli) in human promyelocytic leukemic HL-60 cells. ESR spectroscopy demonstrated the connection between the radical intensity and apoptosis-inducing activity of derivatives of these compounds. When vitamin C and gallic acid were mixed together, the radical intensity and cytotoxic activity of gallic acid was completely scavenged by one or two orders lower concentrations of vitamin C, suggesting the predominant action of vitamin C over gallic acid. When vitamin C and dopamine were mixed together, their radical intensity and apoptosis-inducing activity counteracted with each other. On the other hand, lignins significantly enhanced both the radical intensity and apoptosis-inducing activity of vitamin C. ESR spectroscopy might be applicable for the detection of drug-drug interaction
    Download PDF (7185K)
  • Motokazu KOUNO
    1999 Volume 113 Issue 6 Pages 357-366
    Published: 1999
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    To determine whether local anesthetics affect functions in macrophages, I examined the effects of 5 local anesthetics, lidocaine HCl, mepivacaine HCl, propitocaine HCl, procaine HCl, and tetracaine HCl, on chemotaxis and production of superoxide anion in rat peripheral macrophages. Rats were intraperitoneally injected with 1% glycogen. Peritoneal exudate cells containing macrophages were obtained from the peritoneal cavity 4 days after the administration. Chemotaxis was evaluated using a 48-well microchemotaxis chamber with a polycarbonate membrane filter. Production of superoxide anion was measured spectrophotometrically by a superoxide dismutase-sensitive reduction of ferricytochromec. All of the local anesthetics examined at a dose of 1 mg/ml inhibited (P<0.05) chemotaxis and production of superoxide anion in macrophages. Moreover, pretreatment of macrophage suspensions with mepivacaine HCl, propitocaine HCl, procaine HCl, or tetracaine HCl at a dose of 1 mg/ml resulted in inhibition of the production of superoxide anion. In contrast, pretreatment with lidocaine HCl at this concentration did not significantly affect the production of superoxide anion. These results suggest that all of the local anesthetics examined at a therapeutic concentration inhibit chemotaxis and production of superoxide anion in rat macrophages.
    Download PDF (8421K)
feedback
Top