Biomaterial Database

Prostaglandin E2 induces contraction of liver myofibroblasts by activating EP3 and FP prostanoid receptors. 2009

S Ayabe, and T Murata, and T Maruyama, and M Hori, and H Ozaki

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

OBJECTIVE Increased portal pressure in liver injury results from hypercontraction of perivascular non-parenchymal cells including liver myofibroblasts (MFs). Prostaglandin E2 (PGE2) is the major eicosanoid which is released around the venous system during liver injury, but little is known about their contractile effect on MFs. METHODS Contraction of primary rat liver MFs was measured by a collagen gel contraction assay. Expression of E prostanoid (EP) receptor subtypes was assessed by reverse transcription-polymerase chain reaction. Fura-2 fluorescence was used to determine intracellular Ca2+ concentration ([Ca2+](i)). Phosphorylation of protein kinase C (PKC) was detected by Western blot analysis. RESULTS Liver MFs expressed mRNAs for all four EP receptors. PGE2 induced contraction in a dose- and time-dependent manner, and slightly increased [Ca2+](i) only at high concentrations (10 micromol.L(-1)). An agonist selective for EP(3) receptors, ONO-AE-248, dose-dependently induced MF contraction but did not increase [Ca2+](i). Pretreatment with rottlerin (a specific novel PKC inhibitor) and Ro 31-8425 (a general PKC inhibitor) significantly reduced 1 micromol.L(-1) PGE(2)- or ONO-AE-248-induced contractions. Furthermore, 1 micromol.L(-1) PGE(2) stimulated phosphorylation of PKC isoforms PKCdelta and PKCepsilon. The F prostanoid (FP) receptor antagonist AL8810 abolished the [Ca(2+)](i) elevation and the rapid contraction induced by 10 micromol.L(-1) PGE2. CONCLUSIONS Lower concentrations up to 1 micromol.L(-1) of PGE2 induce liver MF contraction via a [Ca2+](i)-independent PKC-mediated pathway through the EP(3) receptor, while higher concentrations have an additional pathway leading to Ca(2+)-dependent contraction through activating the FP receptor.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011982	Receptors, Prostaglandin	Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).	Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast