Skip to main content
Kent Academic Repository

Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension

Lai, Ying-Ju, Pullamsetti, Soni Savai, Dony, Eva, Weissmann, Norbert, Butrous, Ghazwan S., Banat, Gamal-Andre, Ghofrani, Hossein A., Seeger, Werner, Grimminger, Friedrich, Schermuly, Ralph T. and others. (2008) Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension. American Journal of Respiratory and Critical care Medicine, 178 (2). 188 -196. ISSN 1073-449X. (doi:10.1164/rccm.200710-1519OC) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:14712)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1164/rccm.200710-1519OC

Abstract

Rationale Iloprost is effective for the treatment of pulmonary hypertension. It acts through elevation of CAMP by binding to the prostacyclin receptor (IP receptor). However, there is evidence that patients with severe pulmonary hypertension have decreased expression of the IP receptor in the remodeled pulmonary arterial smooth muscle.

Objectives: We hypothesized that prostanoid receptors other than the IP receptor are involved in signal transduction by iloprost.

Methods: Immunoblotting was used to detect the IP and prostanoid EP4 receptor in lung tissue from patients with idiopathic pulmonary arterial hypertension, and immunohistochemistry was used to detect these receptors in lung sections from rats treated with monocrotaline (MCT28d). Protein and mRNA were isolated from pulmonary arterial smooth muscle cells (PASMCs) from control and MCT28d rats treated with AH6809 (an EP2 receptor antagonist) and AH23848 (an EP4 receptor antagonist) in combination with iloprost. Intracellular cAMP was also assessed in these tissues.

Measurements and Main Results: IP receptor expression was reduced in idiopathic pulmonary arterial hypertension patient lung samples and MCT28d rat lungs compared with the controls. Reverse transcriptase-polymerase chain reaction and immunoblotting of MCT28d rat PASMC extracts revealed scant expression of the IP receptor but stable expression of EP4 receptor, compared with controls. Iloprost-induced elevation in intracellular CAMP in PASMCs was dose-dependently reduced by AH23848, but not by AH6809.

Conclusions: Iloprost mediates vasodilatory functions via the EP4 receptor in the case of low IP receptor expression associated with pulmonary arterial hypertension. This is a previously unrecognized mechanism for iloprost, and illustrates that the EP4 receptor may be a novel therapeutic approach for the treatment of pulmonary arterial hypertension.

Item Type: Article
DOI/Identification number: 10.1164/rccm.200710-1519OC
Uncontrolled keywords: prostanoid EP4 receptor; iloprost; pulmonary artery hypertension
Subjects: R Medicine > R Medicine (General)
Divisions: Divisions > Division for the Study of Law, Society and Social Justice > School of Social Policy, Sociology and Social Research
Depositing User: Louise Dorman
Date Deposited: 18 Apr 2009 10:48 UTC
Last Modified: 16 Nov 2021 09:53 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/14712 (The current URI for this page, for reference purposes)

University of Kent Author Information

Butrous, Ghazwan S..

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.