2025-09-30 ラトガース大学
<関連情報>
- https://www.rutgers.edu/news/scientists-discover-potential-blood-test-asthma-diagnosis-and-severity
- https://www.jci.org/articles/view/186937
喘息患者では血清cAMP値が上昇する
Serum cAMP levels are increased in patients with asthma
Steven S. An, Gaoyuan Cao, Kwangmi Ahn, Jordan Lee, Dae Young Jung, Loren Denlinger, John Fahy, Elliot Israel, Wendy Moore, Brenda Phillips, David Mauger, Sally Wenzel, and Reynold A. Panettieri Jr.
Journal of Clinical Investigation Published January 7, 2025
DOI:https://doi.org/10.1172/JCI186937
To the Editor: As a cornerstone in the treatment of asthma, β2-agonists prevent or reverse the shortening of human airway smooth muscle (HASM), the pivotal cell regulating bronchomotor tone. β2-Agonists act upon β2-adrenoceptor (β2AR) — the cognate Gs-coupled G protein-coupled receptor (Gs-GPCR) expressed on HASM — and activate adenylyl cyclase, which generates 3′,5′-cyclic adenosine monophosphate (cAMP) (1). Increased intracellular cAMP levels ([cAMP]i) consequently stimulate protein kinase A that in turn modulates multiple downstream targets to promote HASM relaxation and reverse airflow obstruction (2).
Classically, the signal transduction evoked by β2ARs is short lived and multiple mechanisms ensure homeostatic regulation of [cAMP]i, with phosphodiesterase (PDE) degradation of cAMP considered to play a dominant role. Using primary HASM cells in culture as a model, we recently reported that β2AR activation evokes cAMP egress to the extracellular space ([cAMP]e) that is long lived in culture, independent of PDE activity, and mediated by ABCC1 (ATP-binding cassette subfamily C member 1) membrane transporter (3). Inhibition of ABCC1 activity or expression decreases cAMP egress, increases [cAMP]i, and enhances HASM relaxation elicited by structurally diverse agonists acting upon Gs-GPCRs (3). These findings suggest a class effect of Gs-GPCR activation and identify ABCC1 as a previously unrecognized cAMP signal response modifier in HASM. Of note, in a small cohort of patients with and without asthma, we detected increased cAMP levels in the blood of patients with asthma (3).
