Src-kinase-dependent epidermal growth factor receptor transactivation in salivary mucin secretion in response to β-adrenergic G-protein-coupled receptor activation

Src-kinase-dependent epidermal growth factor receptor transactivation in salivary mucin secretion... The principal regulatory factors that control the flow and make-up of salivary secretion are neurotransmitters, released by parasympathetic and sympathetic innervation, that trigger activation of G protein-coupled receptors (GPCRs) on the acinar cells of salivary glands and stimulate the generation of soluble second messengers. In this study, we report that activation of GPCR by β-adrenergic agonist leading to stimulation in salivary mucin secretion occurs with the involvement of epidermal growth factor receptor (EGFR). Using [3H]glucosamine-labeled mucous acinar cells of sublingual salivary gland in culture, we show that stimulatory effect of β-adrenergic agonist, isoproterenol, on mucin secretion was inhibited in a concentration-dependent manner by EGFR kinase inhibitor, PD153035, as well as wortmannin, an inhibitor of PI3K. Moreover, both inhibitors caused the impedance in the acinar cell mucin secretory responses to β-adrenergic agonist-generated second messenger, cAMP, as well as adenylate cyclase activator, forskolin. The acinar cell secretory responses to isoproterenol, furthermore, were blunted in a concentration-dependent fashion by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR autophosphorylation. However, no significant alterations in the acinar cell mucin secretory responses to isoproterenol, cAMP or forskolin were attained with an inhibitor of the ERK pathway, PD98059. Our findings underline the role of EGFR as a convergence point in modulation of salivary mucin secretion triggered by β-adrenergic agonist GPCR activation and demonstrate the importance of Src kinase in the EGFR transactivation process. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Inflammopharmacology Springer Journals

Src-kinase-dependent epidermal growth factor receptor transactivation in salivary mucin secretion in response to β-adrenergic G-protein-coupled receptor activation

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Publisher
Brill Academic Publishers
Copyright
Copyright © 2004 by VSP
Subject
Biomedicine; Pharmacology/Toxicology; Allergology; Rheumatology
ISSN
0925-4692
eISSN
1568-5608
D.O.I.
10.1163/1568560042342329
Publisher site
See Article on Publisher Site

Abstract

The principal regulatory factors that control the flow and make-up of salivary secretion are neurotransmitters, released by parasympathetic and sympathetic innervation, that trigger activation of G protein-coupled receptors (GPCRs) on the acinar cells of salivary glands and stimulate the generation of soluble second messengers. In this study, we report that activation of GPCR by β-adrenergic agonist leading to stimulation in salivary mucin secretion occurs with the involvement of epidermal growth factor receptor (EGFR). Using [3H]glucosamine-labeled mucous acinar cells of sublingual salivary gland in culture, we show that stimulatory effect of β-adrenergic agonist, isoproterenol, on mucin secretion was inhibited in a concentration-dependent manner by EGFR kinase inhibitor, PD153035, as well as wortmannin, an inhibitor of PI3K. Moreover, both inhibitors caused the impedance in the acinar cell mucin secretory responses to β-adrenergic agonist-generated second messenger, cAMP, as well as adenylate cyclase activator, forskolin. The acinar cell secretory responses to isoproterenol, furthermore, were blunted in a concentration-dependent fashion by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR autophosphorylation. However, no significant alterations in the acinar cell mucin secretory responses to isoproterenol, cAMP or forskolin were attained with an inhibitor of the ERK pathway, PD98059. Our findings underline the role of EGFR as a convergence point in modulation of salivary mucin secretion triggered by β-adrenergic agonist GPCR activation and demonstrate the importance of Src kinase in the EGFR transactivation process.

Journal

InflammopharmacologySpringer Journals

Published: Aug 1, 2004

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