title: Characterization of GPRA, a novel G protein-coupled receptor related to asthma.
abstract: We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Vendelin
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
authors.forename: Marko
authors.initials: M
authors.lastname: Rehn
authors.forename: Asta
authors.initials: A
authors.lastname: Pirskanen
authors.forename: Anne
authors.initials: A
authors.lastname: Räisänen-Sokolowski
authors.forename: Annika
authors.initials: A
authors.lastname: Laitinen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Laitinen
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology*; D019556:COS Cells; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics; D012326:RNA Splicing; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: C484532:NPSR1 protein, human; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled