Relaxant Effect of Prostaglandin D2-Receptor DP Agonist on Liver Myofibroblast Contraction

• Maruyama Tomoharu

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

• Ayabe Shinya

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

• Murata Takahisa

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

• Hori Masatoshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

• Ozaki Hiroshi

  Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

Bibliographic Information

Other Title

• Prostaglandin D2 induces contraction via thromboxane A2 receptor in rat liver myofibroblasts

Abstract

Increased intrahepatic resistance causes portal hypertension in cirrhosis. Liver myofibroblasts (MFs) are now regarded as the principle cells involved in sinusoidal blood flow regulation. Many other prostaglandin-receptor agonists have been reported to regulate liver MF contraction, but the role of the prostaglandin D₂–receptor DP is unknown. In this study, we investigated the effect of a synthetic agonist of prostanoid DP receptor, BW245C, on contractile properties of primary rat liver MFs. Collagen gel contraction assay revealed that BW245C alone (1 and 10 μM) did not induce contraction but induced cell relaxation. Pretreatment with BW245C (10 μM, 30 min) attenuated bradykinin (100 nM)-induced liver MF contraction. Elevation of [Ca²⁺]_i induced by bradykinin (100 nM) was partially suppressed by BW245C pretreatment (10 μM, 3 min). BW245C (1 and 10 μM) significantly increased intracellular cAMP level in a dose-dependent manner. Pretreatment with forskolin (30 – 300 nM, 30 min) and dibutyryl-cAMP (3 – 30 μM, 30 min) significantly reduced bradykinin-induced contraction. Furthermore, a protein kinase A (PKA) inhibitor KT5720 (10 nM to 1 μM, 30 min) blocked the relaxant effect of BW245C. These results suggest that prostanoid DP receptor agonism inhibits bradykinin-induced [Ca²⁺]_i elevation and contraction through cAMP–PKA signal activation in rat liver MFs.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 116 (2), 197-203, 2011

  The Japanese Pharmacological Society

Keywords

• cirrhosis
• liver myofibroblast
• relaxation
• prostaglandin D<SUB>2</SUB>
• prostanoid DP receptor

Details

• CRID: 1390001205181490304
• NII Article ID: 10029894739
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.10325fp
• DOI: 10.1016/j.ejphar.2008.06.037
• ISSN: 13478648
• ISSN: 13478613
• ISSN: 00142999
• NDL BIB ID: 11122131
• Web Site: http://id.ndl.go.jp/bib/11122131
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11122131
• Web Site: https://api.elsevier.com/content/article/PII:S0014299908006584?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0014299908006584?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2012122855
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed