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Volume 119 (2002)
- Issue 6 Pages 319-
- Issue 5 Pages 273-
- Issue 4 Pages 201-
- Issue 3 Pages 135-
- Issue 2 Pages 65-
- Issue 1 Pages 7-
Volume 119, Issue 5
Displaying 1-5 of 5 articles from this issue
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Review
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Toshio OBATAArticle type: Review
2002 Volume 119 Issue 5 Pages 273-279
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSAdenosine exerts cardioprotective effects on the ischemic myocardium. A flexibly mounted microdialysis apparatus was used to measure the concentration of interstitial adenosine and to assess the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production) in in vivo rat hearts. The level of adenosine during adenosine 5'-adenosine monophosphate (AMP) perfusion serves as an index of the activity of ecto-5'-nucleotidase in the tissue. Endogenous norepinephrine (NE) activates α1-adrenoceptors to lead to the activation of protein kinase C (PKC), which, in turn, activates ecto-5'-nucleotidase via phosphorylation, thereby enhancing the production of interstitial adenosine. Histamine-induced release of NE activates PKC, which increases ecto-5'-nucleotidase activity and augments release of adenosine. Nicorandil, a hybrid of an ATP sensitive K+ (KATP) channel opener and nitrate, increases the level of interstitial adenosine via cGMP-mediated activation of ecto-5'-nucleotidase. Opening of cardiac KATP channels may cause hydroxyl radical (·OH) generation. Nitric oxide (NO) facilitates the production of interstitial adenosine, via activation of ecto-5'-nucleotidase. However, singlet oxygen (1O2) is a very powerful oxidant that causes inactivation of ecto-5'-nucleotidase to result in a decrease in the concentration of adenosine in rat heart. Adenosine plays an important role as a modulator of ischemic reperfusion injury. The production and action of adenosine are intimately linked to the release of NE.
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Hideyuki KOBAYASHI, Hiroki YOKOO, Toshihiko YANAGITA, Akihiko WADAArticle type: Review
2002 Volume 119 Issue 5 Pages 281-286
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSThe brain microvessels are formed by a specialized endothelium and regulate the movement of solutes between blood and brain. The endothelial cells are sealed together by tight junctions and play a role as the blood-brain barrier. The brain microvessels express GLUT1 as the major form of glucose transporter, aquaporin-4 as a water channel, and p-glycoprotein as a xenobiotic transporter. Occludin and claudin-5 have been identified as the components of tight junction. Increasing evidence suggests that the activities of the transporters are regulated by adrenergic nerve activity as well as by bioactive peptides such as adrenomedullin. The regulation of the activity as well as expression of these transporters may become a strategy for prophylaxis and treatment of not only cerebral vascular diseases but also neurodegenerative disorders, developmental abnormalities and aging of the brain.
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Eiichi GOHDAArticle type: Review
2002 Volume 119 Issue 5 Pages 287-294
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSHepatocyte growth factor (HGF) was purified as a potent mitogen for rat hepatocytes in primary culture and is believed to be the most physiological hepatotrophic factor that triggers liver regeneration. HGF is one of the largest disulfide-linked cytokines, consisting of a 60-kDa heavy chain and a 35-kDa light chain. Human HGF is synthesized as a single polypeptide chain precursor of 728 amino acid residues that has an appreciable homology with plasminogen, and it is processed proteolytically to release an N-terminal signal peptide of 31 amino acids and to generate an active heterodimer after secretion. The novel serine protease HGF activator and urokinase-type plasminogen activator (u-PA) are responsible for the latter extracellular processing. HGF stimulates the proliferation of rat hepatocytes in primary culture at concentrations as low as 10 pM. It also stimulates the growth of various epithelial cells, endothelial cells, and some kinds of mesenchymal cells. HGF inhibits the proliferation of several tumor cell lines and induces apoptosis of some of them. It also has motogenic, morphogenic, anti-apoptotic, angiogenic, and immunoregulatory activities. The receptor of HGF is the product of c-met proto-oncogene with tyrosine kinase activity that mediates the transduction of multiple biological signals of HGF. During liver regeneration, HGF gene expression in the liver, spleen, and lung and HGF levels in the blood and liver increase prior to the induction of liver DNA synthesis. Liver regeneration is markedly inhibited by continuous administration of a neutralizing anti-HGF antibody. HGF production in cultured cells is induced by PKC-activating agents, cAMP-elevating agents, PKA-activating agents, growth factors, and inflammatory cytokines; and it is inhibited by TGF-β, glucocorticoids, 1,25-dihydroxyvitamin D3, and retinoic acid. There are many reports on potential application of HGF as a therapeutic agent for organ diseases that are difficult to cure such as liver cirrhosis, chronic renal failure, pulmonary fibrosis, myocardial infarction, and arteriosclerosis obliterans utilizing its potent growth-stimulating activity for a wide variety of cells. ELISA kits for assays of serum and plasma HGF levels are clinically used to prognosticate the development of fulminant hepatic failure.
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Katsuya SUEMARU, Hiroaki ARAKI, Yutaka GOMITAArticle type: Review
2002 Volume 119 Issue 5 Pages 295-300
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSNeuronal nicotinic acetylcholine receptors (nAChR) are a family of ligand-gated ion channels that have a pentameric structure composed of five membrane spanning subunits. Recent progress in clinical and neurochemical studies have shown that neuronal nAChR are involved in some psychiatric disorders such as schizophrenia, depression, and anxiety via its stimulating effect of multiple neurotransmitters. It has been suggested that the high prevalence of smoking in the patients with psychiatric disorders is an attempt to alleviate some psychiatric symptoms using the central stimulatory effect of nicotine (a self-medication effort) or to alleviate the exacerbated symptoms by nicotine withdrawal. Moreover, recent studies with mutant mice lacking specific nAChR subunits and animal models of psychiatric disorders have indicated the psychopharmacological role of individual nAChR subunits in psychiatric disorders. Thus, it is suggested that α7 nAChR is involved in the attention deficit of schizophrenic patients and that α4β2 nAChR is related to nicotine dependence or the withdrawal symptoms.
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Review on New Drug
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Masahiko TANAKAArticle type: Review on New Drug
2002 Volume 119 Issue 5 Pages 301-308
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSThe involvement of oxygen radical species has been implicated in ischemic and post-ischemic brain cell damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; M.W. 174.20, MCI-186, Radicut Injection) has an inhibitory effect on lipid peroxidation by scavenging free radicals and prevents vascular endothelial cell injury. In rat brain ischemic models, post-ischemic treatment with edaravone reduces ·OH production and infarction of the ischemic penumbral area and suppresses delayed neuronal death. It also improves neurological deficits and diminishes deterioration of brain edema observed after ischemia. We investigated the efficacy and safety of edaravone in acute ischemic stroke patients. Edaravone improved the core neurological deficits, impaired activities of daily living, and disability, without serious safety problems. Edaravone was approved in Japan for the treatment of acute brain infarction within 24 h after onset in April, 2001. We hope that edaravone represents a promising neuroprotective agent that can contribute to the treatment of acute ischemic stroke.
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