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

Kobayashi, Koji; Murata, Takahisa; Hori, Masaru; Ozaki, Hiroshi

doi:10.1016/j.ejphar.2011.03.032

Cited by 37 publications

(37 citation statements)

References 31 publications

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“…Similarly, MMP-2-mediated TGF-β1 activation and subsequent matrix-associated protein deposition are also implicated in arterial stiffness in aged arteries (61). Moreover, PGE 2 / EP3-mediated arterial contraction seems to require ROCK activation (62), which may also contribute to the development of PAH.…”

Section: Discussionmentioning

confidence: 99%

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

Lü

Zuo

et al. 2015

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

Lü

Zuo

et al. 2015

J. Clin. Invest.

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“…Among the PGs, prostaglandin E 2 (PGE 2 ), an important and ubiquitously distributed vasoactive eicosanoid, has been reported to be a potent vasodilator in various vessels in both humans and experimental animals [9,43,66]. However, PGE 2 may be a vasoconstrictor in some vessels such as human pulmonary artery [50], guinea pig aorta [26], porcine large cerebral arteries [25], rat aorta [61] and rat mesenteric artery [32]. The actual PGE 2 -mediated vascular response appears to depend on species and vessel type as well as on conditions such as physiological and pathophysiological states.…”

Section: Introductionmentioning

confidence: 98%

Protein kinase C delta contributes to increase in EP3 agonist-induced contraction in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats

Ishida

Matsumoto

Taguchi

et al. 2012

Pflugers Arch - Eur J Physiol

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Prostaglandin E(2) (PGE(2)), an important and ubiquitously present vasoactive eicosanoid, may either constrict or dilate systemic vascular beds. However, little is known about the vascular contractile responsiveness to and signaling pathways for PGE(2) at the chronic stage of type 2 diabetes. We hypothesized that PGE(2)-induced arterial contraction is augmented in type 2 diabetic Goto-Kakizaki (GK) rats via the protein kinase Cδ (PKCδ) pathway. Here, we investigated the vasoconstrictor effects of PGE(2) and of sulprostone (EP1-/EP3-receptor agonist) in rings cut from superior mesenteric arteries isolated from GK rats (37-44 weeks old). In arteries from GK rats (vs. those from age-matched Wistar rats), examined in the presence of a nitric oxide synthase inhibitor: 1) the PGE(2)- and sulprostone-induced vasocontractions (which were not blocked by the selective EP1 receptor antagonist sc19220) were enhanced, and these enhancements were suppressed by rottlerin (selective PKCδ inhibitor) but not by Gö6976 (selective PKCα/β inhibitor); 2) the sulprostone-stimulated phosphorylation of PKCδ (at Thr(505)), which yields an active form, was increased and 3) sulprostone-stimulated caldesmon phosphorylations, which are related to isometric force generation in smooth muscle, were increased. The protein expression of EP3 receptor in superior mesenteric arteries was similar between the two groups of rats. Our data suggest that the diabetes-related enhancement of EP3 receptor-mediated vasocontraction results from activation of the PKCδ pathway. Alterations in EP3 receptor-mediated vasocontraction may be important factors in the pathophysiological influences over arterial tone that are present in diabetic states.

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“…ONO-DI-004, ONO-AE1-259-01, ONO-AE-248, and ONO-AE1-329 (Tajima et al, 2008); PGE 2 and LY798106 (Kobayashi et al, 2011); AH6809 and AH23848 (Goldmann et al, 2010); SU6668 (Reinmuth et al, 2001); genistein (Iovine et al, 2011); FGF-2 (Izikki et al, 2009);MK886 (Ikeda-Matsuo et al, 2010); CAY10404 (Lee et al, 2007); and indomethacin and SC-560 (Fornai et al, 2006).…”

Section: Ah23848 {(7-[5␣-([1s1␣(z)-biphenyl]-4-ylmethoxy)-2␤-(4-morpmentioning

confidence: 99%

Prostaglandin E₂Promotes Wound-Induced Migration of Intestinal Subepithelial Myofibroblasts via EP2, EP3, and EP4 Prostanoid Receptor Activation

Iwanaga

Okada²,

Murata

et al. 2011

J Pharmacol Exp Ther

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Intestinal subepithelial myofibroblasts (ISMFs) are mesenchymal cells that reside in the subepithelial region throughout the intestine. When the intestine is damaged, the migratory and mitotic responses of ISMFs are crucial for wound closure. However, their mechanism of action remains unknown. We have investigated the role of cyclooxygenase (COX) and its metabolite prostaglandin E 2 (PGE 2 ) in the wound repair process of bovine ISMFs. The action of a mechanical scratch in a layer of ISMFs in cell culture elevated the levels of both COX-2 mRNA expression and PGE 2 secretion 1 and 6 h after the event. After 24 h ISMFs had migrated to and reduced the wounded area around the site of the scratch. Treatment with the COX-1/2 inhibitor indomethacin, the COX-2 inhibitor 3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole (CAY10404), or E prostanoid receptor 2 to 4 (EP2-EP4) antagonists significantly inhibited wound repair. Conversely, inhibition of wound closure by indomethicin was reversed by treatment with PGE 2 or agonists of the receptors EP2, EP3, or EP4 but not of EP1. Although EP2 to EP4 stimulation did not influence ISMF proliferation, it did stimulate ISMF migration in the transwell cell migration assay. It is noteworthy that cell migration stimulated by EP2 and EP4 was inhibited by the tyrosine kinase receptor inhibitor genistein and also by (Z)-3-[2,4-dimethyl-5-(2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]-propionic acid (SU6668). However, cell migration stimulated by EP3 was unaffected. Reverse transcription-polymerase chain reaction showed EP2 or EP4 stimulation elevated the level of mRNA expression for fibroblast growth factor-2, which stimulates ISMF migration. Collectively, COX-2-dependent PGE 2 secretion promotes wound healing by ISMFs. PGE 2 -EP3 signaling may directly stimulate ISMF migration. PGE 2 -EP2/4 signaling indirectly stimulates ISMF migration by elevating the level of growth factor secretion.

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

Cited by 37 publications

References 31 publications

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

Protein kinase C delta contributes to increase in EP3 agonist-induced contraction in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats

Prostaglandin E₂Promotes Wound-Induced Migration of Intestinal Subepithelial Myofibroblasts via EP2, EP3, and EP4 Prostanoid Receptor Activation

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

Cited by 37 publications

References 31 publications

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

Protein kinase C delta contributes to increase in EP3 agonist-induced contraction in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats

Prostaglandin E2Promotes Wound-Induced Migration of Intestinal Subepithelial Myofibroblasts via EP2, EP3, and EP4 Prostanoid Receptor Activation

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Prostaglandin E₂Promotes Wound-Induced Migration of Intestinal Subepithelial Myofibroblasts via EP2, EP3, and EP4 Prostanoid Receptor Activation