Heterogeneity in dynamic regulation of intracellular calcium in airway smooth muscle cells

1997 ◽  
Vol 75 (7) ◽  
pp. 878-888 ◽  
Author(s):  
G C Sieck ◽  
M S Kannan ◽  
Y S Prakash
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Dynamic Regulation

scholarly journals Altered CD38/Cyclic ADP-Ribose Signaling Contributes to the Asthmatic Phenotype

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph A. Jude ◽  
Mythili Dileepan ◽  
Reynold A. Panettieri ◽  
Timothy F. Walseth ◽  
Mathur S. Kannan
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Map Kinases ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Cd38 Expression ◽  
Cyclic Adp Ribose

CD38 is a transmembrane glycoprotein expressed in airway smooth muscle cells. The enzymatic activity of CD38 generates cyclic ADP-ribose from β-NAD. Cyclic ADP-ribose mobilizes intracellular calcium during activation of airway smooth muscle cells by G-protein-coupled receptors through activation of ryanodine receptor channels in the sarcoplasmic reticulum. Inflammatory cytokines that are implicated in asthma upregulate CD38 expression and increase the calcium responses to contractile agonists in airway smooth muscle cells. The augmented intracellular calcium responses following cytokine exposure of airway smooth muscle cells are inhibited by an antagonist of cyclic ADP-ribose. Airway smooth muscle cells from CD38 knockout mice exhibit attenuated intracellular calcium responses to agonists, and these mice have reduced airway response to inhaled methacholine. CD38 also contributes to airway hyperresponsiveness as shown in mouse models of allergen or cytokine-induced inflammatory airway disease. In airway smooth muscle cells obtained from asthmatics, the cytokine-induced CD38 expression is significantly enhanced compared to expression in cells from nonasthmatics. This differential induction of CD38 expression in asthmatic airway smooth muscle cells stems from increased activation of MAP kinases and transcription through NF-κB, and altered post-transcriptional regulation through microRNAs. We propose that increased capacity for CD38 signaling in airway smooth muscle in asthma contributes to airway hyperresponsiveness.

Muscarinic inhibition of adenylyl cyclase regulates intracellular calcium in single airway smooth muscle cells

1996 ◽  
Vol 270 (2) ◽  
pp. L208-L214 ◽  
Author(s):  
J. M. Madison ◽  
H. Yamaguchi
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Adenylyl Cyclase ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Airway Smooth Muscle Cells ◽  
Muscarinic Agonists ◽  
Cyclic Monophosphate

To determine whether muscarinic agonists attenuated isoproterenol-stimulated decreases in intracellular calcium concentration ([Ca2+]i), changes in [Ca2+]i were measured in single airway smooth muscle cells using ratiometric analysis of fura 2 fluorescence. Isoproterenol (10(-5) M) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) decreased [Ca2+]i by 24 +/- 3% (P < 0.05, n= 28) and 17 +/- 1% (P < 0.05, n = 6), respectively. The decreased [Ca2+]i in response to isoproterenol was inhibited by propranolol (10(-6) M) and Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) (10-40 microM). In subsequent experiments assessing the effects of muscarinic agonists, isoproterenol did not decrease [Ca2+]i in the presence of carbachol (5 x 10(-8) M) (6 +/- 8% increase; NS, n = 8). To determine the mechanism underlying this inhibitory effect of carbachol, cells were loaded with 4,5-dimethoxy-2-nitrobenzyl adenosine-3',5'-cyclic monophosphate (caged cAMP). For cells loaded with 20 microM caged cAMP, photolysis of caged cAMP decreased basal [Ca2+]i by 28 +/- 3% (P < 0.05, n = 12). In the presence of carbachol (5 x 10(-8) M), photolysis of caged cAMP still induced a 27 +/- 4% decrease in [Ca2+]i (P < 0.05, n = 12). We concluded that a low concentration of carbachol did attenuate isoproterenol-stimulated decreases in [Ca2+]i. Because low concentrations of carbachol attenuated the decreases in [Ca2+]i stimulated by isoproterenol but not the comparable decreases stimulated by cAMP directly, we concluded that the inhibition of adenylyl cyclase activity by muscarinic agonists contributed to the regulation of [Ca2+]i in airway smooth muscle cells. The findings suggested that physiological levels of cholinergic stimulation inhibit adenylyl cyclase, thereby attenuating the effects that beta-adrenergic agonists have on [Ca2+]i.

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

2005 ◽  
Vol 288 (5) ◽  
pp. L773-L788 ◽  
Author(s):  
Deepak A. Deshpande ◽  
Thomas A. White ◽  
Soner Dogan ◽  
Timothy F. Walseth ◽  
Reynold A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Calcium Homeostasis ◽  
Calcium Concentration ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Airway Diseases ◽  
Cyclic Adp Ribose

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.

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