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

62 Citations (Scopus)

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

Fingerprint

Cyclic ADP-Ribose
Muscle
Calcium
Smooth Muscle Myocytes
Endothelin-1
Smooth Muscle
ADP-ribosyl Cyclase
Lung
Methacholine Chloride
Compliance
Acetylcholine
Tissue

Keywords

  • Airway
  • cADPR
  • CD38
  • Responsiveness
  • Smooth muscle

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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

Altered airway responsiveness in CD38-deficient mice. / Deshpande, Deepak A.; White, Thomas A.; Guedes, Alonso G P; Milla, Carlos; Walseth, Timothy F.; Lund, Frances E.; Kannan, Mathur S.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 32, No. 2, 02.2005, p. 149-156.

Research output: Contribution to journalArticle

Deshpande, DA, White, TA, Guedes, AGP, Milla, C, Walseth, TF, Lund, FE & Kannan, MS 2005, 'Altered airway responsiveness in CD38-deficient mice', American Journal of Respiratory Cell and Molecular Biology, vol. 32, no. 2, pp. 149-156. https://doi.org/10.1165/rcmb.2004-0243OC
Deshpande DA, White TA, Guedes AGP, Milla C, Walseth TF, Lund FE et al. Altered airway responsiveness in CD38-deficient mice. American Journal of Respiratory Cell and Molecular Biology. 2005 Feb;32(2):149-156. https://doi.org/10.1165/rcmb.2004-0243OC
Deshpande, Deepak A. ; White, Thomas A. ; Guedes, Alonso G P ; Milla, Carlos ; Walseth, Timothy F. ; Lund, Frances E. ; Kannan, Mathur S. / Altered airway responsiveness in CD38-deficient mice. In: American Journal of Respiratory Cell and Molecular Biology. 2005 ; Vol. 32, No. 2. pp. 149-156.
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