Bronchial hyperresponsiveness: insights into new signaling molecules.
Signaling molecules play a critical role in the pathophysiology of airway diseases. Recent evidence shows that cyclic ADP-ribose (cADPr), an endogenous activator of the ryanodine receptor channel in mammalian cells, modulates agonist-induced calcium responses in airway smooth muscle (ASM) cells. In addition, cADPr-mediated calcium release appears to play an important role in the "non-specific" increased ASM responsiveness to contractile agonists in cytokine-treated cells, a characteristic finding of asthma. Furthermore, other signaling molecules such as Rho/Rho kinase and phosphodiesterase also contribute to bronchial hyperresponsiveness. Thus, a better understanding of these signaling molecules that alter calcium signaling and contractility of ASM might provide new insight into novel therapeutic targets for the control of bronchial hyperresponsiveness.
Amrani
Yassine
Y
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Medical Center, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. amrani@mail.med.upenn.edu
Tliba
Omar
O
Deshpande
Deepak A
DA
Walseth
Timothy F
TF
Kannan
Mathur S
MS
Panettieri
Reynold A
RA
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D020013:Calcium Signaling / Q000502:physiology*; D036563:Cyclic ADP-Ribose / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D016207:Cytokines; D036563:Cyclic ADP-Ribose