Identification and characterization of multiple corticotropin-releasing factor type 2 receptor isoforms in the rat esophagus.

Abstract:

:The rat esophagus shares some cellular features with skin squamous epithelium and striated muscle that express high levels of corticotropin-releasing factor type 2 (CRF2) receptors or their cognate ligand urocortin (Ucn) 1, 2, and 3. We investigated the expression and cell signaling of CRF2 receptors and ligands in the rat esophagus and lower esophageal sphincter (LES) by RT-PCR and quantitative PCR in normal and corticosterone-treated whole esophageal tissue, laser capture microdissected layers, and isolated esophageal cells. The expression of CRF2 receptor protein and intracellular cAMP and ERK1/2 responses to CRF agonists and CRF2 antagonist were determined in cultured esophageal cells and HEK-293 cells transfected with CRF2b receptors. CRF2 was abundantly expressed in the mucosa and longitudinal muscle layers of the esophagus and LES, whereas CRF1 expression was scarce. CRF2b wild-type transcript was predominantly expressed in the esophagus, and in addition, several new CRF2 splice variants including six CRF2a isoforms were identified. Expression of Ucn 1, Ucn 2, and to a smaller extent Ucn 3, but not CRF mRNA, was detected in the esophagus and LES. Ucn 1 and Ucn 2 stimulated dose-dependent cAMP production and ERK1/2 phosphorylation in the esophageal cells, whereas CRF and CRF1 agonist, cortagine, had less potent effects. In addition, Ucn 2-stimulated cAMP and ERK responses were blocked by the CRF2 antagonist, astressin2-B. These data established the presence of a prominent CRF2 signaling system in the esophagus and LES-encompassing multiple CRF2 receptor variants and Ucn, suggesting a functional role in secretomotor activity and epithelial and muscle cell proliferation.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Wu SV,Yuan PQ,Wang L,Peng YL,Chen CY,Taché Y

doi

10.1210/en.2006-0565

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

1675-87

issue

4

eissn

0013-7227

issn

1945-7170

pii

en.2006-0565

journal_volume

148

pub_type

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