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Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease
- Source :
- American Journal of Physiology-Lung Cellular and Molecular Physiology. 291:L1005-L1017
- Publication Year :
- 2006
- Publisher :
- American Physiological Society, 2006.
-
Abstract
- A genetic contribution to asthma susceptibility is well recognized, and linkage studies have identified a large number of genes associated with asthma pathogenesis. Recently, a locus encoding a seven-transmembrane protein was shown to be associated with asthma in founder populations. The expression of the protein GPRA (G protein-coupled receptor for asthma susceptibility) in human airway epithelia and smooth muscle, and its increased expression in a mouse model of asthma, suggested that a gain-of-function mutation in this gene increased the disease risk. However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered. A possible explanation for this finding became apparent upon reexamination of the expression of this gene. In contrast to initial studies, our analyses failed to detect expression of GPRA in human lung tissue or in mice with allergic lung disease. We identify a single parameter that distinguishes GPRA-deficient and wild-type mice. Whereas the change in airway resistance in response to methacholine was identical in control and GPRA-deficient mice, the mutant animals showed an attenuated response to thromboxane, a cholinergic receptor-dependent bronchoconstricting agent. Together, our studies fail to support a direct contribution of GPRA to asthma pathogenesis. However, our data suggest that GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease. This interpretation is supported by high levels of GPRA expression in the brain and its recent identification as the neuropeptide S receptor.
- Subjects :
- Lipopolysaccharides
Pulmonary and Respiratory Medicine
Ovalbumin
Physiology
Hypothalamus
Gene Expression
Locus (genetics)
Disease
Biology
Retina
Receptors, G-Protein-Coupled
Bronchoconstrictor Agents
Pathogenesis
Mice
Genetic linkage
Physiology (medical)
medicine
Animals
Humans
Anaphylaxis
Lung
Gene
Neuropeptide S receptor
Asthma
Mice, Inbred BALB C
Muscle, Smooth
Pneumonia
Cell Biology
medicine.disease
Mice, Mutant Strains
respiratory tract diseases
Mice, Inbred C57BL
Disease Models, Animal
Phenotype
medicine.anatomical_structure
Acute Disease
Immunology
Respiratory Mechanics
Subjects
Details
- ISSN :
- 15221504 and 10400605
- Volume :
- 291
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Accession number :
- edsair.doi.dedup.....a61ec348c59ec66eeb420e2da40494c1