Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides.

摘要: Purinergic regulation of airway innate defence activities is in part achieved by the release nucleotides from epithelial cells. However, mechanisms nucleotide are poorly understood. We have previously demonstrated that ATP released ionomycin-stimulated goblet cells coordinately with mucin exocytosis, suggesting as a co-cargo molecule mucin-containing granules. now demonstrate protease-activated-receptor (PAR) agonists also stimulate simultaneous mucins and PAR-mediated were dependent on intracellular Ca2+ actin cytoskeleton reorganization since BAPTA AM, cytochalasin D, inhibitors Rho myosin light chain kinases blocked both responses. To test hypothesis co-released granules, we measured composition isolated granules purified based their MUC5AC VAMP-8 content density gradients. Mucin contained ATP, but levels ADP AMP within exceeded nearly 10-fold ATP. Consistent this finding, apical secretions PAR-stimulated relatively high ADP/AMP, which could not be accounted for solely hydrolysis. Thus, contribute to source extracellular AMP. Direct ADP/AMP likely provide major surface adenosine signal paracrine faction ciliated cell A2b receptors activate ion/water secretion appropriately hydrate cell-released mucins.