Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Search
Advanced search
OR
Browse
Search
Volume 123, Issue 1
Displaying 1-4 of 4 articles from this issue
Show all abstracts
    • |<
    • <
    • 1
    • >
    • >|
Reviews: Physiology and Pharmacology of Prostaglandin D2 and Related Molecules
  • Functional analyses of lipocalin-type and hematopoietic prostaglandin D synthases
    Yoshihiro URADE, Naomi EGUCHI, Kosuke ARITAKE, Osamu HAYAISHI
    Article type: Reviews
    2004 Volume 123 Issue 1 Pages 5-13
    Published: 2004
    Released on J-STAGE: December 23, 2003
    DOIhttps://doi.org/10.1254/fpj.123.5
    JOURNAL FREE ACCESS
    Show abstractHide abstract
    Prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH2 to PGD2, which acts as an endogeous somnogen and an allergic mediator. There are two distinct types of PGDS: one is lipocalin-type PGDS (L-PGDS) localized in the central nervous system, male genitals, and heart; and the other is hematopoietic PGDS (H-PGDS) in mast cells and Th2 lymphocytes. L-PGDS is the same as beta-trace, a major protein in human cerebrospinal fluid, and is also secreted into the seminal plasma and plasma. The L-PGDS concentration in various body fluids is useful as a marker for various diseases such as renal failure and coronary atherosclerosis. H-PGDS is a cytosolic enzyme and is a member of the Sigma class of glutathione S-transferase. We determined the X-ray crystallographic structures of H-PGDS and L-PGDS. We also generated the gene-knockout (KO) mice and the human enzyme-overexpressing transgenic mice for each PGDS. L-PGDS-KO mice lacked PGE2-induced tactile allodynia and rebound of non-rapid eye movement sleep after sleep deprivation. Human L-PGDS-overexpressing transgenic mice showed an increase in non-rapid eye movement sleep due to accumulation of PGD2 in the brain after tail clipping. H-PGDS-KO mice showed an allergic reaction weaker than that of the wild-type mice.
    View full abstract
    Download PDF (274K)
  • Prostaglandin D2 in allergy: PGD2 has dual receptor systems
    Hiroyuki HIRAI
    Article type: Reviews
    2004 Volume 123 Issue 1 Pages 15-22
    Published: 2004
    Released on J-STAGE: December 23, 2003
    DOIhttps://doi.org/10.1254/fpj.123.15
    JOURNAL FREE ACCESS
    Show abstractHide abstract
    Allergic inflammations feature an accumulation of T helper 2 (Th2) cells, eosinophils, and basophils into the inflamed sites and are often triggered by antigen-IgE mediated activation of mast cells that secret a variety of mediators. Therefore, the mast cell is known as a conductor cell in allergic inflammations. Prostaglandin (PG) D2 is the major prostanoid secreted from the activated mast cell and has long been implicated in allergic diseases. The involvement of PGD2 in allergic inflammation has been corroborated by several studies. Two PGD2 receptors are known as the DP receptor and CRTH2. CRTH2 differs from DP in its signal pathways: CRTH2 is coupled with Gi-type G protein and DP is coupled with Gs-type G protein. It was reported that DP-deficient mice subjected to ovalbumin-induced asthma model systems showed suppressed allergic reactions. Functions of CRTH2 in vivo have not been clear, but CRTH2 mediates PGD2-dependent cell migration and the activation of Th2 cells, eosinophils, and basophils. Therefore, the CRTH2 signal seems to promote allergic disease. The findings from these in vivo and vitro studies suggest that PGD2 secreted from activated mast cells may be involved in the formation and/or maintenance of allergic inflammations through its dual receptor systems.
    View full abstract
    Download PDF (156K)
  • PGD2/L-PGDS system in hypertension and renal injury
    Yoshio UEHARA
    Article type: Reviews
    2004 Volume 123 Issue 1 Pages 23-33
    Published: 2004
    Released on J-STAGE: December 23, 2003
    DOIhttps://doi.org/10.1254/fpj.123.23
    JOURNAL FREE ACCESS
    Show abstractHide abstract
    Prostaglandin D2 (PGD2) and its metabolites bind to the intracellular PPARs to regulate vasoactive substances involved in vascular remodeling through regulation of mRNAs transcription as well as through receptor-mediated mechanisms. PGD2 decreases inducible NO, PAI-1, endothelin, and VCAM expression through inhibition to NFkB, STAT, or AP-1 transcription factors, which are regulated by cytokines/immune system. Moreover, transfer of L-PGDS (PGD2 synthase) into the intracellular space of EC or SMC increases intracellular PGD2, thereby decreasing these substances. PGD2 attenuates in vivo organ injury mediated by cytokines and the immune system. The pretreatment with PGD2 attenuates the liver damage and hemodynamic collapse following LPS. Dahl salt-sensitive rats, with decreased PGD2 in the outer medulla of the kidney, are prone to hypertensive kidney injury. Serum L-PGDS level is increased in renal dysfunction through a decrease in glomerular filtration. L-PGDS in urine may be derived from a failure of tubular reabsorption or from in situ synthesis. Urinary L-PGDS excretion markedly increases in the early stage of kidney injury, and urinary L-PGDS is a useful predictor of the forthcoming renal injury. Indeed, urinary L-PGDS precedes clinically overt proteinuria or other parameters indicating renal dysfunction in hypertension, primary renal diseases, and diabetes in humans. PGD2/L-PGDS system is a Cinderella of vascular biology.
    View full abstract
    Download PDF (754K)
  • Physiology and pharmacology of the prostaglandin J2 family
    Yoshikazu MIWA, Yoji TABA, Megumi MIYAGI, Toshiyuki SASAGURI
    Article type: Reviews
    2004 Volume 123 Issue 1 Pages 34-40
    Published: 2004
    Released on J-STAGE: December 23, 2003
    DOIhttps://doi.org/10.1254/fpj.123.34
    JOURNAL FREE ACCESS
    Show abstractHide abstract
    The prostaglandin (PG) J2 family including PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) are metabolites of PGD2. They had been known as powerful inhibitors of cell proliferation and viral replication until 15d-PGJ2 was found to be a natural ligand for peroxisome proliferator-activated receptor γ (PPARγ). Since then, several new pharmacological actions of the PGJ2 family have been found, such as pro- and anti-apoptotic effects, cell differentiation-inducing effects, and inhibitory effects on inflammatory processes, whether they depend on PPARγ or not. We reported that the PGJ2 family, particularly 15d-PGJ2, inhibits cell proliferation by reducing the expression of G1 cyclins and inducing the expression of cyclin-dependent kinase inhibitor p21 and moreover, induces cell differentiation in vascular smooth muscle cells. In vascular endothelial cells, we found that 15d-PGJ2 inhibits apoptotic cell death at least in part by the induction of the inhibitor of apoptosis protein c-IAP1. More importantly, physiological levels of laminar fluid shear stress loaded on endothelial cells upregulate the expression of lipocalin-type PGD2 synthase, which converts PGH2 to PGD2, the precursor of the PGJ2 family. Based on these results, we have hypothesized that the PGJ2 family synthesized in vascular wall plays an important physiological role to protect vascular cells from atherogenic stimuli.
    View full abstract
    Download PDF (153K)
    • |<
    • <
    • 1
    • >
    • >|
feedback
 Top