Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Airway submucosal glands are sites of high expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel and contribute to fluid homeostasis in the lung. However, the molecular mechanisms of gland ion and fluid transport are poorly defined. Here, submucosal gland serous acinar cells were isolated from murine airway, identified by immunofluorescence and gene expression profiling, and used in physiological studies. Stimulation of isolated acinar cells with carbachol (CCh), histamine or ATP was associated with marked decreases in cell volume (20 +/- 2% within 62 +/- 5 s) that were tightly correlated with increases in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) as revealed by simultaneous DIC and fluorescent indicator dye microscopy. Simultaneous imaging of cell volume and the Cl(-)-sensitive fluorophore SPQ indicated that the 20% shrinkage was associated with a fall of [Cl(-)](i) from 65 mm to 28 mm, reflecting loss of 67% of cell Cl(-) content, accompanied by parallel efflux of K(+). Upon agonist removal, [Ca(2+)](i) relaxed and the cells swelled back to resting volume via a bumetanide-sensitive Cl(-) influx pathway, likely to be NKCC1. Accordingly, agonist-induced serous acinar cell shrinkage and swelling are caused by activation of solute efflux and influx pathways, respectively, and cell volume reflects the secretory state of these cells. In contrast, elevation of cAMP failed to elicit detectible volume responses, or enhance those induced by submaximal [CCh], because the magnitude of the changes were likely to be below the threshold of detection using optical imaging. Finally, when stimulated with cholinergic or cAMP agonists, cells from mice that lacked CFTR, as well as wild-type cells treated with a CFTR inhibitor, exhibited identical rates and magnitudes of shrinkage and Cl(-) efflux compared with control cells. These results provide insights into the molecular mechanisms of salt and water secretion by lung submucosal glands, and they suggest that while murine submucosal gland fluid secretion in response to cholinergic stimulation can originate from CFTR-expressing serous acinar cells, it is not dependent upon CFTR function.
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PMID:Optical imaging of Ca2+-evoked fluid secretion by murine nasal submucosal gland serous acinar cells. 1752 16

The serous acini of airway submucosal glands are important for fluid secretion in the lung. Serous cells are also sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. However, the mechanisms of serous cell fluid secretion remain poorly defined. In this study, serous acinar cells were isolated from porcine bronchi and studied using optical techniques previously used to examine fluid secretion in rat parotid and murine nasal acinar cells. When stimulated with the cholinergic agonist carbachol, porcine serous cells shrank by approximately 20% (observed via DIC microscopy) after a profound elevation of intracellular [Ca(2+)] ([Ca(2+)](i); measured by simultaneous fura 2 fluorescence imaging). Upon removal of agonist and relaxation of [Ca(2+)](i) to resting levels, cells swelled back to resting volume. Similar results were observed during stimulation with histamine and ATP, and elevation of [Ca(2+)](i) was found to be necessary and sufficient to activate shrinkage. Cell volume changes were associated with changes in [Cl(-)](i) (measured using SPQ fluorescence), suggesting that shrinkage and swelling are caused by loss and gain of intracellular solute content, respectively, likely reflecting changes in the secretory state of the cells. Shrinkage was inhibited by niflumic acid but not by GlyH-101, suggesting Ca(2+)-activated secretion is mediated by alternative non-CFTR Cl(-) channels, possibly including Ano1 (TMEM16A), expressed on the apical membrane of porcine serous cells. Optimal cell swelling/solute uptake required activity of the Na(+)K(+)2Cl(-) cotransporter and Na(+)/H(+) exchanger, both of which are expressed on the basolateral membrane of serous acini and likely contribute to sustaining transepithelial secretion.
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PMID:Mechanisms of Ca2+-stimulated fluid secretion by porcine bronchial submucosal gland serous acinar cells. 1996 83