|
|
|
|||||||
|
|||||||||
(Received for publication, April 10, 1996, and in revised form, October 11, 1996)
From the Cholinergic agonists stimulate isotonic fluid
secretion in the parotid gland. This process is driven by the apical
exit of Cl
Volume 272, Number 1,
Issue of January 3, 1997
pp. 287-294
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
and
Division of Cell Biology, Hospital for Sick
Children, Toronto, M5G 1X8, Canada and the 
Department of
Physiology, McGill University, Montreal, H3G 1Y6 Canada
, which enters the cells partly via
Cl/HCO3 exchange across the
basolateral membrane. Acidification of the cytosol by the extrusion of
HCO3 is prevented by the concomitant activation
of the Na+/H+ exchanger (NHE), which is
directly activated by cholinergic stimulation. Multiple isoforms of the
NHE have been described in mammalian cells, but the particular
isoform(s) present in salivary glands and their mechanism of activation
have not been defined. Reverse transcriptase-polymerase chain reaction
with isoform-specific primers was used to establish that NHE-1 and
NHE-2, but not NHE-3 or NHE-4, are expressed in parotid glands. The
presence of NHE-1 was confirmed by immunoblotting and
immunofluorescence, which additionally demonstrated that this isoform
is abundant in the basolateral membrane of acinar cells. The
predominant role of NHE-1 in carbachol-induced
Na+/H+ exchange was established
pharmacologically using HOE694, an inhibitor with differential potency
toward the individual isoforms. Because muscarinic agonists induce
stimulation of protein kinases in acinar cells, we assessed the role of
phosphorylation in the activation of the antiport. Immunoprecipitation
experiments revealed that, although NHE-1 was phosphorylated in the
resting state, no further phosphorylation occurred upon treatment with
carbachol. Similar phosphopeptide patterns were observed in control and
carbachol-treated samples. Together, these findings indicate that
NHE-1, the predominant isoform of the antiporter in the basolateral
membrane of acinar cells, is activated during muscarinic stimulation by
a phosphorylation-independent event. Other processes, such as
association of Ca2+-calmodulin complexes to the cytosolic
domain of the antiporter, may be responsible for the activation of
Na+/H+ exchange.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. J. Lee, J. M. Harlow, M. P. Limberis, J. M. Wilson, and J. K. Foskett HCO3- Secretion by Murine Nasal Submucosal Gland Serous Acinar Cells during Ca2+-stimulated Fluid Secretion J. Gen. Physiol., July 1, 2008; 132(1): 161 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Lee, M. P. Limberis, M. F. Hennessy, J. M. Wilson, and J. K. Foskett Optical imaging of Ca2+-evoked fluid secretion by murine nasal submucosal gland serous acinar cells J. Physiol., August 1, 2007; 582(3): 1099 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Han, K. H. Kim, M. J. Jo, J. H. Lee, J. Yang, R. B. Doctor, O. W. Moe, J. Lee, E. Kim, and M. G. Lee Shank2 Associates with and Regulates Na+/H+ Exchanger 3 J. Biol. Chem., January 20, 2006; 281(3): 1461 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Lee, J. H. Nam, and S. J. Kim Muscarinic activation of Na+-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G822 - G831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Murao, A. Shimizu, K. Hosoi, A. Iwagaki, K.-Y. Min, G.-i. Kishima, T. Hanafusa, T. Kubota, M. Kato, H. Yoshida, et al. Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells: Ca2+ regulation of Na+-H+ exchange Exp Physiol, March 1, 2005; 90(2): 203 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sugita, C. Hirono, and Y. Shiba Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl- Movements in Salivary Acinar Cells J. Gen. Physiol., June 28, 2004; 124(1): 59 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Roussa, S. L. Alper, and F. Thévenod Immunolocalization of Anion Exchanger AE2, Na+/H+ Exchangers NHE1 and NHE4, and Vacuolar Type H+-ATPase in Rat Pancreas J. Histochem. Cytochem., April 1, 2001; 49(4): 463 - 474. [Abstract] [Full Text]
|
|
|
|
|
|
J. E. Melvin, H.-V. Nguyen, K. Nehrke, C. M. Schreiner, K. G. Ten Hagen, and W. Scott Targeted disruption of the Nhe1 gene fails to inhibit {beta}1-adrenergic receptor-induced parotid gland hypertrophy Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G694 - G700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-V. Nguyen, G. E Shull, and J. E Melvin Muscarinic receptor-induced acidification in sublingual mucous acinar cells: loss of pH recovery in Na+-H+ exchanger-1 deficient mice J. Physiol., February 15, 2000; 523(1): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gekle, K. Drumm, S. Mildenberger, R. Freudinger, B. Gassner, and S. Silbernagl Inhibition of Na+-H+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum J. Physiol., November 1, 1999; 520(3): 709 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Evans, S. M. Bell, P. J. Schultheis, G. E. Shull, and J. E. Melvin Targeted Disruption of the Nhe1 Gene Prevents Muscarinic Agonist-induced Up-regulation of Na+/H+ Exchange in Mouse Parotid Acinar Cells J. Biol. Chem., October 8, 1999; 274(41): 29025 - 29030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ishibashi, A. Dinudom, K. F. Harvey, S. Kumar, J. A. Young, and D. I. Cook Na+-H+ exchange in salivary secretory cells is controlled by an intracellular Na+ receptor PNAS, August 17, 1999; 96(17): 9949 - 9953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Takahashi, J.-i. Abe, B. Gallis, R. Aebersold, D. J. Spring, E. G. Krebs, and B. C. Berk p90RSK Is a Serum-stimulated Na+/H+ Exchanger Isoform-1 Kinase. REGULATORY PHOSPHORYLATION OF SERINE 703 OF Na+/H+ EXCHANGER ISOFORM-1 J. Biol. Chem., July 16, 1999; 274(29): 20206 - 20214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Park, J. A. Olschowka, L. A. Richardson, C. Bookstein, E. B. Chang, and J. E. Melvin Expression of multiple Na+/H+ exchanger isoforms in rat parotid acinar and ductal cells Am J Physiol Gastrointest Liver Physiol, February 1, 1999; 276(2): G470 - G478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.E. Melvin Chloride Channels and Salivary Gland Function Critical Reviews in Oral Biology & Medicine, January 1, 1999; 10(2): 199 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Lee, P. J Schultheis, M. Yan, G. E Shull, C. Bookstein, E. Chang, M. Tse, M. Donowitz, K. Park, and S. Muallem Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct J. Physiol., December 1, 1998; 513(2): 341 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Shrode, B. S. Gan, S. J. A. D'Souza, J. Orlowski, and S. Grinstein Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage Am J Physiol Cell Physiol, August 1, 1998; 275(2): C431 - C439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Frohlich and M. Karmazyn The Na-H exchanger revisited: an update on Na-H exchange regulation and the role of the exchanger in hypertension and cardiac function in health and disease Cardiovasc Res, November 1, 1997; 36(2): 138 - 148. [Full Text] [PDF]
|
|
|
|
|
|
K. Park, R. L. Evans, G. E. Watson, K. Nehrke, L. Richardson, S. M. Bell, P. J. Schultheis, A. R. Hand, G. E. Shull, and J. E. Melvin Defective Fluid Secretion and NaCl Absorption in the Parotid Glands of Na+/H+ Exchanger-deficient Mice J. Biol. Chem., July 13, 2001; 276(29): 27042 - 27050. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |