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Am J Physiol Lung Cell Mol Physiol 288: L773-L788, 2005; doi:10.1152/ajplung.00217.2004
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INVITED REVIEW

CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle

Deepak A. Deshpande,1 Thomas A. White,2 Soner Dogan,1 Timothy F. Walseth,3 Reynold A. Panettieri,4 and Mathur S. Kannan1

Departments of 1Veterinary and Biomedical Sciences and 3Pharmacology, University of Minnesota, Saint Paul; 2Allergic Diseases Research Laboratory, Mayo Clinic, Rochester, Minnesota; and 4Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

The contractility of airway smooth muscle cells is dependent on dynamic changes in the concentration of intracellular calcium. Signaling molecules such as inositol 1,4,5-trisphosphate and cyclic ADP-ribose play pivotal roles in the control of intracellular calcium concentration. Alterations in the processes involved in the regulation of intracellular calcium concentration contribute to the pathogenesis of airway diseases such as asthma. Recent studies have identified cyclic ADP-ribose as a calcium-mobilizing second messenger in airway smooth muscle cells, and modulation of the pathway involved in its metabolism results in altered calcium homeostasis and may contribute to airway hyperresponsiveness. In this review, we describe the basic mechanisms underlying the dynamics of calcium regulation and the role of CD38/cADPR, a novel pathway, in the context of airway smooth muscle function and its contribution to airway diseases such as asthma.

ryanodine receptor; calcium oscillations; inflammatory cytokines; muscarinic receptors; 12.6-kDa FK506-binding protein


Address for reprint requests and other correspondence: M. S. Kannan, Dept. of Veterinary and Biomedical Sciences, College of Veterinary Medicine, 205 Veterinary Science, 1971 Commonwealth Ave., St. Paul, MN 55108 (E-mail: kanna001{at}umn.edu)




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