Effects of specific prostanoid EP receptor agonists on cell proliferation and intracellular Ca2+ concentrations in human airway smooth muscle cells

Mori, Akemi; Ito, Satoru; Morioka, Masataka; Aso, Hirotomo; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori

doi:10.1016/j.ejphar.2011.03.001

Cited by 28 publications

(22 citation statements)

References 49 publications

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“…There are no previous reports demonstrating functional expression of EP1 receptor in human ASM cells [18, 80, 88]. Indeed, either EP1 receptor agonist SC19220 or ONO-DI-004, did not affect proliferation of human ASM cells [18, 80].…”

Section: Pge2-mediated Modulation Of Asm Functionmentioning

confidence: 97%

“…Recent studies have explored the concept of EP receptor targeting as a means of improving the therapeutic potential of E prostanoids and the expression of mRNA for EP2, EP3, and EP4 receptors has been identified in human ASM cells [80, 82, 87]. Burgess et al demonstrated that ASM cells isolated from patients with asthma had more expression of EP3 and EP2 receptors than those from control subjects [82].…”

Section: Pge2-mediated Modulation Of Asm Functionmentioning

confidence: 99%

“…Indeed, either EP1 receptor agonist SC19220 or ONO-DI-004, did not affect proliferation of human ASM cells [18, 80]. In contrast, EP1 receptor activation increases ASM tone in guinea pigs [89] and reduces the broncho-dilatory function of β-agonists receptor in mouse ASM cells [90].…”

Section: Pge2-mediated Modulation Of Asm Functionmentioning

confidence: 99%

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cAMP regulation of airway smooth muscle function

Billington¹,

Ojo²,

Penn³

et al. 2013

Pulmonary Pharmacology & Therapeutics

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189

144

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Agonists activating β2-adrenoceptors (β2ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E2 and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β2ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β2AR desensitization, and recent findings regarding the manner in which β2ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β2ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD.

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Section: Pge2-mediated Modulation Of Asm Functionmentioning

confidence: 97%

Section: Pge2-mediated Modulation Of Asm Functionmentioning

confidence: 99%

See 1 more Smart Citation

cAMP regulation of airway smooth muscle function

Billington¹,

Ojo²,

Penn³

et al. 2013

Pulmonary Pharmacology & Therapeutics

Self Cite

189

144

View full text Add to dashboard Cite

show abstract

“…EP4 is highly expressed in airway smooth muscle cells, pulmonary fibroblasts, and smooth muscle cells of the pulmonary vein. In particular, together with the EP2 receptor, EP4 transcripts and proteins are abundantly expressed in human airway smooth muscle cells (Bradbury et al, 2005;Clarke et al, 2005;Mori et al, 2011;Benyahia et al, 2012). It is also known that EP4 activation causes potent relaxation in human and rat bronchial preparations (Lydford and McKechnie, 1994;Benyahia et al, 2012).…”

Section: +mentioning

confidence: 99%

“…Buckley et al (2011) reported that PGE 2 -induced relaxation of the airway was mediated through EP4 in humans and rats. Mori et al (2011) demonstrated that PGE 2 inhibited fetal bovine serum-induced proliferation of human airway smooth muscle cells via EP4 receptor activation. Taken together, these findings suggest that the EP4 receptor could potentially be a therapeutic target in treating pulmonary diseases such as asthma and chronic obstructive pulmonary disease.…”

Section: +mentioning

confidence: 99%

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

227

257

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Reorientation dynamics and structural interdependencies of actin, microtubules and intermediate filaments upon cyclic stretch application

et al. 2018

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Any cell within a tissue is constantly confronted with a variety of mechanical stimuli. Sensing of these diverse stimuli plays an important role in cellular regulation. Besides shear stress, cells of the vascular endothelium are particularly exposed to a permanent cyclic straining originating from the interplay of outwards pushing blood pressure and inwards acting contraction by smooth musculature. Perpendicular alignment of cells as structural adaptation to this condition is a basic prerequisite in order to withstand deformation forces. Here, we combine live cell approaches with immunocytochemical analyses on single cell level to closely elucidate the mechanisms of cytoskeletal realignment to cyclic strain and consolidate orientation analyses of actin fibres, microtubules (MTs) and vimentin. We could show that strain-induced reorientation takes place for all cytoskeletal systems. However, all systems are characterized by their own, specific reorientation time course with actin filaments reorienting first followed by MTs and finally vimentin. Interestingly, in all cases, this reorientation was faster than cell body realignment which argues for an active adaptation mechanism for all cytoskeletal systems. Upon actin destabilization, already smallest alterations in actin kinetics massively hamper cell morphology under strain and therefore overall reorientation. Depolymerization of MTs just slightly influences actin reorientation velocity but strongly affects cell body reorientation.

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Effects of specific prostanoid EP receptor agonists on cell proliferation and intracellular Ca2+ concentrations in human airway smooth muscle cells

Cited by 28 publications

References 49 publications

cAMP regulation of airway smooth muscle function

cAMP regulation of airway smooth muscle function

The Prostanoid EP4 Receptor and Its Signaling Pathway

Reorientation dynamics and structural interdependencies of actin, microtubules and intermediate filaments upon cyclic stretch application

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