Am J Physiol Cell Physiol AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 284: C988-C998, 2003. First published December 21, 2002; doi:10.1152/ajpcell.00582.2001
0363-6143/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/4/C988    most recent
00582.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (23)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kanno, H.
Right arrow Articles by Dartt, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanno, H.
Right arrow Articles by Dartt, D. A.
Vol. 284, Issue 4, C988-C998, April 2003

Cholinergic agonists transactivate EGFR and stimulate MAPK to induce goblet cell secretion

Harumi Kanno1,2,*, Yoshitaka Horikawa1,2,*, Robin R. Hodges1, Driss Zoukhri1, Marie A. Shatos1, Jose D. Rios1, and Darlene A. Dartt1

1 Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114; and 2 Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan 078-8510

Conjunctival goblet cells are the primary source of mucins in the mucous layer, the innermost layer of the tear film. Conjunctival goblet cell mucin secretion is under neural control because exogenous addition of parasympathetic agonists stimulates goblet cell secretion. To elucidate the intracellular signal pathways used by cholinergic agonists to stimulate goblet cell mucin secretion, we determined whether p42/p44 mitogen-activated protein kinase (MAPK) is activated during cholinergic agonist-stimulated mucin secretion. Rat conjunctiva was removed, preincubated with or without antagonists, and stimulated with the cholinergic agonist carbachol (10-4 M). Carbachol statistically significantly stimulated the phosphorylation of MAPK in a time- and concentration-dependent manner. U-0126, an inhibitor of MAPK activation, completely inhibited both the activation of MAPK and goblet cell secretion stimulated by carbachol. The M1 muscarinic antagonist pirenzepine, the M2 muscarinic antagonist gallamine, and the M1/M3 muscarinic receptor antagonist N-(3-chloropropyl)-4-piperidinyl diphenylacetate (4-DAMP) also inhibited carbachol-stimulated MAPK activation. Increasing the intracellular Ca2+ concentration with a Ca2+ ionophore increased MAPK activation, and chelation of extracellular Ca2+ inhibited carbachol-stimulated activation. Carbachol also increased tyrosine phosphorylation of Pyk2, p60Src, and the epidermal growth factor receptor (EGFR). The Src inhibitor PP1 and the EGFR inhibitor AG-1478 completely inhibited carbachol-stimulated MAPK activation. AG-1478 also inhibited goblet cell secretion. We conclude that carbachol transactivates the EGFR to activate MAPK, leading to conjunctival goblet cell secretion. In addition, carbachol also activates Pyk2 and p60Src that could play a role in the transactivation of the EGFR.

signal transduction; muscarinic receptors; conjunctiva; Pyk2; p60Src

* H. Kanno and Y. Horikawa contributed equally to this work.




This article has been cited by other articles:


Home page
 IOVSHome page
M. A. Shatos, J. Gu, R. R. Hodges, K. Lashkari, and D. A. Dartt
ERK/p44p42 Mitogen-Activated Protein Kinase Mediates EGF-Stimulated Proliferation of Conjunctival Goblet Cells in Culture
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3351 - 3359.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. L. Lin, B. Zhu, W. Zhang, H. Dang, B.-X. Zhang, M. S. Katz, and C.-K. Yeh
Distinct pathways of ERK activation by the muscarinic agonists pilocarpine and carbachol in a human salivary cell line
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1454 - C1464.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
I. S. T. Bos, R. Gosens, A. B. Zuidhof, D. Schaafsma, A. J. Halayko, H. Meurs, and J. Zaagsma
Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison
Eur. Respir. J., October 1, 2007; 30(4): 653 - 661.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. Dillard, R. A. Wetsel, and S. M. Drouin
Complement C3a Regulates Muc5ac Expression by Airway Clara Cells Independently of Th2 Responses
Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1250 - 1258.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. C. Snider and K. E. Meier
Receptor transactivation cascades. Focus on "Effects of {alpha}1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells"
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C1 - C3.
[Full Text] [PDF]

Home page
 IOVSHome page
R. R. Hodges, J. D. Rios, J. Vrouvlianis, I. Ota, D. Zoukhri, and D. A. Dartt
Roles of Protein Kinase C, Ca2+, Pyk2, and c-Src in Agonist Activation of Rat Lacrimal Gland p42/p44 MAPK.
Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3352 - 3359.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Kim, A. J. Schein, and J. A. Nadel
E-cadherin promotes EGFR-mediated cell differentiation and MUC5AC mucin expression in cultured human airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L1049 - L1060.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. A. Shatos, J. D. Rios, Y. Horikawa, R. R. Hodges, E. L. Chang, C. R. Bernardino, P. A. D. Rubin, and D. A. Dartt
Isolation and Characterization of Cultured Human Conjunctival Goblet Cells
Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2477 - 2486.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online