Altered airway responsiveness in CD38-deficient mice

Am J Respir Cell Mol Biol. 2005 Feb;32(2):149-56. doi: 10.1165/rcmb.2004-0243OC. Epub 2004 Nov 19.


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 < or = 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase / genetics
  • ADP-ribosyl Cyclase / metabolism*
  • ADP-ribosyl Cyclase 1
  • Acetylcholine / pharmacology
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / genetics
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Cyclic ADP-Ribose / metabolism
  • Endothelin-1 / pharmacology
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle Contraction / genetics
  • Muscle Contraction / physiology
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Respiratory System / metabolism*
  • Vasodilator Agents / pharmacology


  • Antigens, CD
  • Endothelin-1
  • Membrane Glycoproteins
  • Vasodilator Agents
  • Cyclic ADP-Ribose
  • ADP-ribosyl Cyclase
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1
  • Acetylcholine
  • Calcium