| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell and Molecular Physiology
2 Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599, USA
SPOC1 airway goblet cells secrete mucin in response to P2Y2 receptor agonists and to secretagogues, phorbol 12-myristate 13-acetate (PMA) and ionomycin, which mobilize elements of the phospholipase C pathway, PKC and Ca2+, respectively. Previous studies demonstrated that mucin secretion from SLO-permeabilized, EGTA-buffered SPOC1 cells was stimulated by PMA at low Ca2+ levels (< 0.1 µM), consistent with the notion that regulated exocytosis may occur by Ca2+-independent pathways. We tested the alternative hypothesis that PMA-induced mucin secretion is, in fact, a Ca2+-dependent process under the conditions of low bulk Ca2+, one that is permitted in the typical SLO-permeabilized cell model by the slow binding kinetics of EGTA. Both IP3 and elevated bulk Ca2+ activated mucin secretion in SPOC1 cells buffered by EGTA, suggesting that IP3 generates a local Ca2+ gradient in the vicinity of the secretory granules to the degree necessary to trigger exocytosis. BAPTA, which binds Ca2+ approximately 100-fold faster than EGTA, diminished IP3-induced mucin release over a range of concentrations by 
69%, yet maintained an essentially normal mucin secretory response to elevated bulk Ca2+ in permeabilized SPOC1 cells. BAPTA also diminished the mucin secretory response of permeabilized cells to PMA, relative to the EGTA-buffered control: at PMA below 30 nM, BAPTA abolished the secretory response, and at higher concentrations it was reduced significantly relative to the EGTA-buffered controls. PMA-induced secretion in EGTA was insensitive to heparin. These results suggest that Ca2+ is released locally during PMA-induced exocytosis, by an IP3-independent mechanism.
(Received 21 June 2004;
accepted after revision 23 June 2004;
first published online 24 June 2004)
Corresponding author C. W. Davis: 6009 Thurston-Bowles, University of North Carolina, Chapel Hill, NC 27599-7248. Email: cwdavis{at}med.unc.edu
This article has been cited by other articles:
|
|
 |
|
  Y. Zhu, C. Ehre, L. H. Abdullah, J. K. Sheehan, M. Roy, C. M. Evans, B. F. Dickey, and C. W. Davis Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways J. Physiol., April 1, 2008; 586(7): 1977 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ehre, Y. Zhu, L. H. Abdullah, J. Olsen, K. I. Nakayama, K. Nakayama, R. O. Messing, and C. W. Davis nPKC{varepsilon}, a P2Y2-R downstream effector in regulated mucin secretion from airway goblet cells Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1445 - C1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Abdullah and C. W. Davis Regulation of airway goblet cell mucin secretion by tyrosine phosphorylation signaling pathways Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L591 - L599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Rossi, W. C. Salmon, M. Chua, and C. W. Davis Calcium signaling in human airway goblet cells following purinergic activation Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L92 - L98. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. J. Young, C.-X. Sun, C. M. Evans, B. F. Dickey, and M. R. Blackburn A3 Adenosine Receptor Signaling Contributes to Airway Mucin Secretion after Allergen Challenge Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 549 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ehre, A. H. Rossi, L. H. Abdullah, K. De Pestel, S. Hill, J. C. Olsen, and C. W. Davis Barrier role of actin filaments in regulated mucin secretion from airway goblet cells Am J Physiol Cell Physiol, January 1, 2005; 288(1): C46 - C56. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
