alpha 1-Adrenergic and cholinergic agonists activate MAPK by separate mechanisms to inhibit secretion in lacrimal gland

1  Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114; and 2  Department of Ophthalmology, Asahikawa Medical College, Asahikawa 078-8510, Japan The purpose of this study was to determine the role of p42/p44 mitogen-activated protein k...

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Published in:American Journal of Physiology: Cell Physiology 2003-01, Vol.284 (1), p.C168-C178
Main Authors: Ota, Isao, Zoukhri, Driss, Hodges, Robin R, Rios, Jose D, Tepavcevic, Vanja, Raddassi, Isabelle, Chen, Li Li, Dartt, Darlene A
Format: Article
Language:English
Subjects:
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists - pharmacology
Animals
Cholinergic Agonists - pharmacology
Dose-Response Relationship, Drug
Enzyme Activation - drug effects
Enzyme Activation - physiology
Enzyme Inhibitors - pharmacology
Epithelial Cells - drug effects
Epithelial Cells - enzymology
Epithelial Cells - secretion
Lacrimal Apparatus - drug effects
Lacrimal Apparatus - enzymology
Lacrimal Apparatus - secretion
Male
Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Rats
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - metabolism
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Summary:1  Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114; and 2  Department of Ophthalmology, Asahikawa Medical College, Asahikawa 078-8510, Japan The purpose of this study was to determine the role of p42/p44 mitogen-activated protein kinase (MAPK) in 1 -adrenergically and cholinergically stimulated protein secretion in rat lacrimal gland acinar cells and the pathways used by these agonists to activate MAPK. Acini were isolated by collagenase digestion and incubated with the 1 -adrenergic agonist phenylephrine or the cholinergic agonist carbachol, and activation of MAPK and protein secretion were then measured. Phenylephrine and carbachol activated MAPK in a time- and concentration-dependent manner. Inhibition of MAPK significantly increased phenylephrine- and carbachol-induced protein secretion. Inhibition of EGF receptor (EGFR) with AG1478, an inhibitor of the EGFR tyrosine kinase activity, significantly increased phenylephrine- but not carbachol-induced protein secretion. Whereas phenylephrine-induced activation of MAPK was completely inhibited by AG1478, activation of MAPK by carbachol was not. Phenylephrine stimulated tyrosine phosphorylation of the EGFR, whereas carbachol stimulated p60 Src , and possibly Pyk2, to activate MAPK. We conclude that, in the lacrimal gland, activation of MAPK plays an inhibitory role in 1 -adrenergically and cholinergically stimulated protein secretion and that these agonists use different signaling mechanisms to activate MAPK. signal transduction; Pyk2; Src * I. Ota and D. Zoukhri contributed equally to this work.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00151.2002