title: Genomic organization and regulation of a human 7-helix transmembrane receptor which is expressed in pulmonary epithelial cells and induced in hypoxia.
abstract: The genetic, regulatory, and tissue-specific characterization of G-protein-coupled receptors is substantial since it contributes to the identification of the natural ligand which may influence basic physiological processes and cell function. Here we explored the genomic structure of a human orphan seven-transmembrane receptor which presents the human homologue of a receptor which has been controversially identified as a rat adrenomedullin receptor subtype. Based on the cDNA sequence a 3.4 kb genomic DNA fragment was isolated. Sequencing of the fragment and comparison studies revealed an intron of 544 bp in the 5' untranslated region, followed by a second exon encoding the receptor protein of 404 amino acids. The gene is localized on chromosome 12q. The 5' regulatory region contains several SP1, AP2, and CAAT sites as well as hypoxia responsive elements (HRE) both in the 5' and 3' regulatory region. RT-PCR with intron spanning primers demonstrated mRNA signals in various tissues, especially in lung. Characterizing the histological expression pattern in lung sections by nonisotopic in situ hybridization, a strong signal of receptor mRNA was identified in pulmonary epithelial cells of bronchi and alveoli. Analysis of the two human pulmonary epithelial cell lines, H23 and A549, showed significant mRNA induction of this receptor subtype in hypoxia.
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University, Klinikstrasse 36, D-35392 Giessen, Germany. joerg.haenze@innere.med.uni-giessen.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Hänze
authors.forename: David A
authors.initials: DA
authors.lastname: Groneberg
authors.forename: Frank
authors.initials: F
authors.lastname: Rose
authors.forename: Anika
authors.initials: A
authors.lastname: Hanisch
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Christian
authors.initials: C
authors.lastname: Peiser
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Axel
authors.initials: A
authors.lastname: Fischer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
mesh_terms: D015687:Cell Hypoxia; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008168:Lung / Q000166:cytology; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C450520:seven-transmembrane G-protein-coupled receptor