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Published on: April 13, 2010
Altered airway responsiveness in CD38-deficient mice
Deepak A Deshpande1, Thomas A White, Alonso G P Guedes
1Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Avenue, Saint Paul, MN 55108, USA.
American Journal of Respiratory Cell and Molecular Biology
|November 24, 2004
Summary
CD38/cyclic ADP-ribose (cADPR) signaling is crucial for airway smooth muscle (ASM) tone. Mice lacking CD38 show reduced responsiveness, indicating CD38
Area of Science:
- Physiology
- Immunology
- Biochemistry
Background:
- Cyclic ADP-ribose (cADPR) is a key regulator of intracellular calcium mobilization in airway smooth muscle (ASM).
- Agonist-induced calcium elevation in ASM cells is critical for regulating airway tone.
- The role of CD38, an enzyme involved in cADPR synthesis, in ASM function was not fully understood.
Purpose of the Study:
- To investigate the functional significance of the CD38/cADPR signaling pathway in regulating airway smooth muscle tone.
- To determine the contribution of CD38 to agonist-induced intracellular calcium responses in ASM cells.
Main Methods:
- Utilized CD38-deficient (cd38(-/-)) mice and wild-type littermate controls.
- Assessed airway responsiveness to methacholine by measuring lung resistance and dynamic compliance.
- Measured intracellular calcium responses to acetylcholine and endothelin-1 in isolated ASM cells.
- Quantified cADPR levels and ADP-ribosyl cyclase activity in lung tissue.
Main Results:
- CD38-deficient mice exhibited significantly lower airway responsiveness to methacholine compared to wild-type controls.
- ASM cells from cd38(-/-) mice showed markedly reduced intracellular calcium responses to acetylcholine and endothelin-1.
- Pharmacological inhibition of cADPR attenuated calcium responses in wild-type ASM cells but not in cd38(-/-) cells.
- Lung tissue from cd38(-/-) mice displayed very low cADPR levels and absent ADP-ribosyl cyclase activity.
Conclusions:
- CD38 is essential for cADPR synthesis in the lung.
- The CD38/cADPR pathway plays a significant role in modulating airway smooth muscle tone and responsiveness.
- This pathway influences airway function by regulating agonist-induced intracellular calcium elevation in ASM cells.

