Selectively targeting prostanoid E (EP) receptor-mediated cell signalling pathways: Implications for lung health and disease

Lebender, LF; Prünte, L; Rumzhum, NN; Ammit, AJ

Selectively targeting prostanoid E (EP) receptor-mediated cell signalling pathways: Implications for lung health and disease

Lebender, LF Prünte, L Rumzhum, NN Ammit, AJ

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Publication Type:: Journal Article
Citation:: Pulmonary Pharmacology and Therapeutics, 2018, 49 pp. 75 - 87
Issue Date:: 2018-04-01

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Field	Value	Language
dc.contributor.author	Lebender, LF	en_US
dc.contributor.author	Prünte, L	en_US
dc.contributor.author	Rumzhum, NN	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.date.available	2020-05-25T19:02:15Z
dc.date.issued	2018-04-01	en_US
dc.identifier.citation	Pulmonary Pharmacology and Therapeutics, 2018, 49 pp. 75 - 87	en_US
dc.identifier.issn	1094-5539	en_US
dc.identifier.uri	http://hdl.handle.net/10453/122339
dc.description.abstract	© 2018 Elsevier Ltd Arachidonic acid is metabolized by cyclooxygenases (COX-1 and COX-2) into various prostanoids which exert different functions in mammalian physiology. One of these prostanoids, prostaglandin E 2 (PGE 2 ), interacts with four different G protein-coupled receptors, named EP 1 , EP 2 , EP 3 and EP 4 , to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE 2 is responsible for a large variety of beneficial and disadvantageous effects. We have recently achieved a greater understanding of the biology of prostanoid E receptors and the potential for specific drug targeting with the advent of potent and selective EP receptor agonists and antagonists. This has important implications for lung health and disease as PGE 2 -mediated EP receptor activation impacts upon migration of airway smooth muscle cells, airway microvascular leak, tone regulation of pulmonary blood vessels, mast cell degranulation, bronchodilatation, cough, angiogenesis and airway inflammation, to name a few. In this review, we overview the EP receptor family and the related signalling pathways, summarize a variety of EP 1-4 receptor agonists and antagonists, provide an overview of pharmacological tools used to implicate EP receptor function in the context of respiratory health and disease and finally highlight some of the more selective pharmacological reagents that have recently been developed. The availability of selective pharmacological agonists and antagonists for the distinct EP receptors, as well as the development of specific prostanoid receptor knock-out mice, offer hitherto unattainable opportunities for achieving an in depth understanding of the role and function of PGE 2 in respiratory disease and the exciting potential of targeting EP receptors more broadly.	en_US
dc.relation.ispartof	Pulmonary Pharmacology and Therapeutics	en_US
dc.relation.isbasedon	10.1016/j.pupt.2018.01.008	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Lung Diseases	en_US
dc.subject.mesh	Arachidonic Acid	en_US
dc.subject.mesh	Receptors, Prostaglandin E	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Drug Development	en_US
dc.title	Selectively targeting prostanoid E (EP) receptor-mediated cell signalling pathways: Implications for lung health and disease	en_US
dc.type	Journal Article
utslib.citation.volume	49	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	49	en_US

Abstract:

© 2018 Elsevier Ltd Arachidonic acid is metabolized by cyclooxygenases (COX-1 and COX-2) into various prostanoids which exert different functions in mammalian physiology. One of these prostanoids, prostaglandin E 2 (PGE 2 ), interacts with four different G protein-coupled receptors, named EP 1 , EP 2 , EP 3 and EP 4 , to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE 2 is responsible for a large variety of beneficial and disadvantageous effects. We have recently achieved a greater understanding of the biology of prostanoid E receptors and the potential for specific drug targeting with the advent of potent and selective EP receptor agonists and antagonists. This has important implications for lung health and disease as PGE 2 -mediated EP receptor activation impacts upon migration of airway smooth muscle cells, airway microvascular leak, tone regulation of pulmonary blood vessels, mast cell degranulation, bronchodilatation, cough, angiogenesis and airway inflammation, to name a few. In this review, we overview the EP receptor family and the related signalling pathways, summarize a variety of EP 1-4 receptor agonists and antagonists, provide an overview of pharmacological tools used to implicate EP receptor function in the context of respiratory health and disease and finally highlight some of the more selective pharmacological reagents that have recently been developed. The availability of selective pharmacological agonists and antagonists for the distinct EP receptors, as well as the development of specific prostanoid receptor knock-out mice, offer hitherto unattainable opportunities for achieving an in depth understanding of the role and function of PGE 2 in respiratory disease and the exciting potential of targeting EP receptors more broadly.

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http://hdl.handle.net/10453/122339