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INVITED REVIEW

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

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

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