Altered airway responsiveness in CD38-deficient mice

Deepak A. Deshpande, Thomas A. White, Alonso G P Guedes, Carlos Milla, Timothy F. Walseth, Frances E. Lund, Mathur S. Kannan

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Cyclic ADP-ribose (cADPR) mobilizes calcium from intracellular stores and contributes to agonist-induced intracellular calcium elevation in airway smooth muscle (ASM). In this study we determined the functional role of CD38/cADPR signaling in the regulation of airway tone using CD38 deficient (cd38 -/-) mice. The responsiveness to different doses of methacholine, as determined by changes in lung resistance and dynamic compliance, was significantly (P ≤ 0.05) lower in cd38-/- mice compared with wild-type controls. To determine the mechanism responsible for the reduced responsiveness, we measured the intracellular calcium responses to contractile agonists in ASM cells. In ASM cells isolated from cd38-/- mice, the intracellular calcium responses to acetylcholine and endothelin-1 were significantly lower than in controls. Pretreatment of ASM cells with a cADPR antagonist resulted in attenuated intracellular calcium responses to endothelin-1 in cells isolated from wild-type mice, but not in those isolated from the cd38-/- mice. Very low cADPR levels and no detectable ADP-ribosyl cyclase activity were observed in lung tissue from cd38 -/- mice, suggesting that CD38 is a critical source for cADPR synthesis. The results of the present study demonstrate that CD38/cADPR contributes to airway smooth muscle tone and responsiveness through its effects on agonist-induced elevation of intracellular calcium in ASM cells.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume32
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Keywords

  • Airway
  • cADPR
  • CD38
  • Responsiveness
  • Smooth muscle

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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  • Cite this

    Deshpande, D. A., White, T. A., Guedes, A. G. P., Milla, C., Walseth, T. F., Lund, F. E., & Kannan, M. S. (2005). Altered airway responsiveness in CD38-deficient mice. American Journal of Respiratory Cell and Molecular Biology, 32(2), 149-156. https://doi.org/10.1165/rcmb.2004-0243OC