Effects of the nitric oxide/cGMP system compared with the cAMP system on airway mucus secretion in the rat

Bredenbröker, Dirk; Dyarmand, Darius; Meingast, Uta; Fehmann, Hans-Christoph; Staats, Petra; Wichert, P. von; Wagner, U.

doi:10.1016/s0014-2999(00)00918-3

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…7 and 8) and with our previous results from SPOC1 cells (2), both of which showed NO-and/or cGMP-active agents to be without effect. Mucin secretion from submucosal glands is also either unaffected or inhibited by NO (8). One general problem with the studies claiming NO/cGMP responsiveness is that the cultures used exhibited relatively low secretory responses (less than onefold relative to baseline; see above), which can easily hinder data analysis.…”

Section: Mucin Secretion From Hbe Cultures Vs Xenograftsmentioning

confidence: 99%

Regulation of mucin secretion from human bronchial epithelial cells grown in murine hosted xenografts

Conway¹,

Bartolotta²,

Abdullah³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Studies of regulated mucin secretion from goblet cells in primary cultures of human bronchial epithelial (HBE) cells have suffered, generally, from poor signal-to-noise ratios, with reported secretory responses of <100% (less than onefold) relative to baseline. Using, instead, HBE cells grown as xenografts in the backs of nude mice, we found that UTP (100 micro M) stimulated strong mucin secretory responses from isolated, luminally perfused preparations. The peak response (10 min) for 11 control experiments (37 xenografts) was 3.3 +/- 0.05-fold relative to baseline, and the time-integrated response (60 min) was 23.4 +/- 0.5-fold. Because responses to ATP and UTP were approximately equal, an apical membrane P2Y(2)-receptor (R) is suggested. Additionally, ADP activated mucin release from HBE xenografts, whereas UDP and 2-methlythio-ADP did not, a pattern of response inconsistent with known purinoceptors. Hence, either a novel receptor to ADP is suggested or there is significant conversion of ADP to ATP by ecto-adenylate kinase activity. Adenosine and a nitric oxide donor were without effect. Consistent with P2Y(2)-R coupling to phospholipase C, HBE xenografts responded to ionomycin and PMA; however, they were recalcitrant to forskolin and chlorophenylthio-cAMP, and to 8-bromo-cGMP. Hence, human airway goblet cells, like those of other species, appear to be regulated primarily via phospholipase C pathways, activated particularly by apical membrane P2Y(2)-R agonists.

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Section: Mucin Secretion From Hbe Cultures Vs Xenograftsmentioning

confidence: 99%

Regulation of mucin secretion from human bronchial epithelial cells grown in murine hosted xenografts

Conway¹,

Bartolotta²,

Abdullah³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In the airways, the effects of ␤-adrenergic agonists and cAMP on smooth muscle relaxation and on the inflammatory mediators in mucosal secretions in asthmatics are well described (20). cAMP-mediated effects on ciliary beat frequency (21)(22)(23) and cystic fibrosis transmembrane conductance regulator activation (24) contribute to regulation of mucociliary transport and the aqueous surface layer, and in animal models prolonged increases in intracellular cAMP increase airway secretions (25). However, little is known about the overall effect of cAMP on transport proteins that may contribute to generation or modulation of the airway surface layer (20).…”

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confidence: 99%

cAMP Has Distinct Acute and Chronic Effects on Aquaporin-5 in Lung Epithelial Cells

Sidhaye

Hoffert

King

2005

Journal of Biological Chemistry

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Aquaporin-5 (AQP5) is present on the apical membrane of epithelial cells in various secretory glands as well as on the apical membrane of the airway epithelium, airway submucosal glands, and type 1 pneumocytes, where it can participate in respiratory tract water homeostasis. We examined the effects of cAMP on AQP5 distribution and abundance. When AQP5-expressing mouse lung epithelial cells were treated with cAMP or the ␤-adrenergic agonist terbutaline, a biphasic AQP5 response was observed. Short term (minutes) exposure to cAMP produced internalization of AQP5 off of the membrane and a decrease in protein abundance. Both of these responses were blocked by inhibition of protein kinase A and the decrease in abundance was blocked by chloroquine, indicating lysosome-mediated degradation. Sustained cAMP exposure (hours) produced an increase in membrane localization and increased abundance; these effects were also blocked by protein kinase A inhibition. The ␤-adrenergic agonist terbutaline produced changes in AQP5 abundance in mouse trachea and lung, consistent with our findings in cultured epithelial cells. Purified AQP5 protein was phosphorylated by protein kinase A but not protein kinase C or casein kinase II, and aquaporin-5 was phosphorylated in cultured cells after long term (but not short term) exposure to cAMP. These studies indicate that cAMP and ␤-adrenergic agonists produce distinct short and long term effects on AQP5 distribution and abundance that may contribute to regulation of lung water homeostasis.Aquaporins are water-specific membrane channel proteins that participate in a wide array of physiologic processes (1). The presence or absence of an aquaporin is the primary determinant of membrane osmotic water permeability. 1 is an apical membrane water channel found at several sites in mammals, including corneal and pancreatic epithelium, secretory cells in salivary and lacrimal glands, and airway submucosal glands, bronchial epithelium, and type I pneumocytes of the respiratory tract (2-5). Studies of isolated salivary gland epithelial cells (6, 7) and type I pneumocytes (8) demonstrate that AQP5 expression confers high level membrane water permeability. An in vivo role for AQP5 in water homeostasis is strongly indicated by studies of AQP5-null mice, which have reduced salivary (6, 7), sweat (9), and airway submucosal gland secretions (10) as well as by recent investigation of persons with Sjögren's syndrome, in whom disrupted AQP5 membrane targeting probably contributes to the clinical hallmarks of dry eyes and dry mouth (11,12).Information regarding the regulation of abundance and distribution of AQP5 is relatively limited. Stimuli such as tumor necrosis factor-␣ (13) and adenoviral infection (14) have been shown to reduce AQP5 expression, whereas hypertonic stress increases AQP5 in cultured lung epithelial cells as well as in lungs and secretory glands of hyperosmolar rats (15). Pilocarpine-stimulated recruitment of AQP5 to the plasma membrane of salivary gland epithelial cells has been proposed (16)...

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“…However, there have been only a few studies investigating the role of NO in mucus secretion with conflicting results. On the one hand, NO inhibited mucus secretion in ferret trachea in vitro [23] and on the other hand, it had a stimulatory role in the mucus secretion in isolated submucosal gland from feline trachea [24] or it had no effect on the mucus secretion in the rat trachea [25]. …”

Section: Discussionmentioning

confidence: 99%

Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways

Song¹,

Kang²,

Yoo³

et al. 2007

Respir Res

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Background: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogenactivated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells.

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Effects of the nitric oxide/cGMP system compared with the cAMP system on airway mucus secretion in the rat

Cited by 11 publications

References 23 publications

Regulation of mucin secretion from human bronchial epithelial cells grown in murine hosted xenografts

Regulation of mucin secretion from human bronchial epithelial cells grown in murine hosted xenografts

cAMP Has Distinct Acute and Chronic Effects on Aquaporin-5 in Lung Epithelial Cells

Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways

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