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

Maruyama, Takafumi; Murata, Takahisa; Ayabe, Shin-ichi; Hori, Masaru; Ozaki, Hiroshi

doi:10.1016/j.ejphar.2008.06.037

Cited by 9 publications

(11 citation statements)

References 35 publications

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“…Treatment with a prostanoid DP-receptor agonist BW245C induced moderate relaxation in liver MFs (1 μM BW245C, −9.93 ± 4.89%; 10 μM BW245C, −14.8 ± 5.56%; n = 4; 3 h after treatment). These data are consistent with our previous observations (8).…”

Section: Bw245c Induces Relaxation In Rat Liver Mfssupporting

confidence: 83%

“…Prostanoid DP and CRTH2 receptors have a role in mediating the biological effect of PGD 2 . We previously demonstrated that liver MFs express both prostanoid DP and CRTH2 receptors and that prostanoid DP-receptor agonism causes MF relaxation under the non-stimulated control (8). Here we showed that the prostanoid DP-receptor agonist BW245C markedly reduces the contractile effect of BK and other contractile agents in liver MFs (Fig.…”

Section: Discussionsupporting

confidence: 48%

“…Cells between passage 3 and 6 were used for experiments. As we previously reported, isolated cells from rat liver expressed α-SMA, fibulin-2 and interleukin-6 at the mRNA level (8). These have been suggested as specific markers for MFs (12,13).…”

Section: Cell Isolation and Culturementioning

confidence: 67%

“…Therefore PGD 2 has emerged as a crucial factor in liver diseases. We previously reported that PGD 2 induces liver MF contraction with an increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) through prostanoid TP receptor, whereas direct prostanoid DP-receptor stimulation induces relaxation in non-stimulated MFs (8). However, the counteraction to the contractile stimuli and the downstream signal path-ways of prostanoid DP-receptor agonism are still unknown in the liver MFs.…”

Section: Introductionmentioning

confidence: 99%

“…Contraction of liver MFs was examined as previously described (8,14). In brief, collagen gels were prepared by mixing 70% type I collagen from porcine tendon (Nitta Gelatin, Osaka), 20% 5 × DMEM and 10% 0.05 N NaOH under ice-cold conditions (final collagen concentration, 2.1 mg/ml).…”

Section: Collagen Gel Contraction Assaymentioning

confidence: 99%

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

et al. 2011

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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 D 2 -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 [Ca 2+ ] 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 [Ca 2+ ] i elevation and contraction through cAMP-PKA signal activation in rat liver MFs.

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Section: Bw245c Induces Relaxation In Rat Liver Mfssupporting

confidence: 83%

Section: Discussionsupporting

confidence: 48%

Section: Cell Isolation and Culturementioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Collagen Gel Contraction Assaymentioning

confidence: 99%

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

et al. 2011

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Diverse effects of prostaglandin E2 on vascular contractility

et al. 2013

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Prostaglandin E₂ (PGE₂) is a major prostanoid produced under inflammatory situations. There have been controversial reports showing contractile or relaxant effect of PGE₂ on vascular tone in various types of blood vessels. Thus, it is still elusive whether and how PGE₂ modulates vascular tone. We here assessed the effects of PGE₂ on vascular contractility using different types of vasculatures isolated form rat. In endothelium-denuded aortas and mesenteric arteries, PGE₂ (1 nM-10 μM) concentration-dependently enhanced the contraction elicited by K(+) (35.4 mM) or norepinephrine (10 nM). In pulmonary arteries, PGE₂ did not alter the both-induced contraction. Tail arteries were relaxed by a low dose of PGE₂ (1-100 nM), but this response shifted to contraction by the higher dose of PGE₂ (300 nM-10 μM). There are four types of PGE₂ receptors EP1-4. RT-PCR showed that aortas and mesenteric arteries abundantly expressed EP3, while tail arteries abundantly expressed EP4. We next revealed that selective EP3 agonism enhanced the contraction in mesenteric arteries, whereas EP4 agonism induced relaxation in tail arteries. Taken together, PGE₂ causes different contractile responses depending on the type of vascular bed. This phenomenon may be due to the difference in expression pattern and activity of EP receptors.

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Prostaglandin E2-prostanoid EP3 signal induces vascular contraction via nPKC and ROCK activation in rat mesenteric artery

Kobayashi

Murata

Hori

et al. 2011

European Journal of Pharmacology

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

Cited by 9 publications

References 35 publications

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

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

Diverse effects of prostaglandin E2 on vascular contractility

Prostaglandin E2-prostanoid EP3 signal induces vascular contraction via nPKC and ROCK activation in rat mesenteric artery

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