Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease

Irving C. Allen, Amy J. Pace, Leigh A. Jania, Julie G. Ledford, Anne M. Latour, John N. Snouwaert, Virginie Bernier, Rino Stocco, Alex G. Therien, Beverly H. Koller

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)L1005-L1017
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number5
DOIs
StatePublished - Nov 23 2006
Externally publishedYes

Keywords

  • Allergic lung disease
  • Anaphylaxis
  • G protein-coupled receptor
  • Neuropeptide S

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Allen, I. C., Pace, A. J., Jania, L. A., Ledford, J. G., Latour, A. M., Snouwaert, J. N., Bernier, V., Stocco, R., Therien, A. G., & Koller, B. H. (2006). Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease. American Journal of Physiology - Lung Cellular and Molecular Physiology, 291(5), L1005-L1017. https://doi.org/10.1152/ajplung.00174.2006