Selectively targeting prostanoid E (EP) receptor-mediated cell signalling pathways: Implications for lung health and disease.
Pulm Pharmacol Ther
; 49: 75-87, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29408043
ABSTRACT
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 E2 (PGE2), interacts with four different G protein-coupled receptors, named EP1, EP2, EP3 and EP4, to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE2 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 PGE2-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 EP1-4 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 PGE2 in respiratory disease and the exciting potential of targeting EP receptors more broadly.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Prostaglandina E
/
Desenvolvimento de Medicamentos
/
Pneumopatias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pulm Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Austrália