EGF inhibits muscarinic receptor-mediated calcium signaling in a human salivary cell line

Bin Xian Zhang, Chih Ko Yeh, Tazuko K. Hymer, Meyer D. Lifschitz, Michael S. Katz

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The effects of epidermal growth factor (EGF) on intracellular calcium ([Ca2+](i)) responses to the muscarinic agonist carbachol were studied in a human salivary cell line (HSY). Carbachol (10-4 M)-stimulated [Ca2+](i) mobilization was inhibited by 40% after 48-h treatment with 5 x 10-10 M EGF. EGF also reduced carbachol-induced [Ca2+](i) in Ca2+-free medium and Ca2+ influx following repletion of extracellular Ca2+. Under Ca2+-free conditions, thapsigargin, an inhibitor of Ca2+ uptake to internal stores, induced similar [Ca2+](i) signals in control and EGF-treated cells, indicating that internal Ca2+ stores were unaffected by EGF; however, in cells exposed to thapsigargin, Ca2+ influx following Ca2+ repletion was reduced by EGF. Muscarinic receptor density, assessed by binding of the muscarinic receptor antagonist L-[benzilic-4,4'-3HCN]quinuclidinyl benzilate ([3H]QNB), was decreased by 20% after EGF treatment. Inhibition of the carbachol response by EGF was not altered by phorbol ester-induced downregulation of protein kinase C (PKC) but was enhanced upon PKC activation by a diacylglycerol analog. Phosphorylation of mitogen-activated protein kinase (MAP kinase) and inhibition of the carbachol response by EGF were both blocked by the MAP kinase pathway inhibitor PD-98059. The results suggest that EGF decreases carbachol-induced Ca2+ release from internal stores and also exerts a direct inhibitory action on Ca2+ influx. A decline in muscarinic receptor density may contribute to EGF inhibition of carbachol responsiveness. The inhibitory effect of EGF is mediated by the MAP kinase pathway and is potentiated by a distinct modulatory cascade involving activation of PKC. EGF may play a physiological role in regulating muscarinic receptor-stimulated salivary secretion.

Original languageEnglish (US)
Pages (from-to)C1024-C1033
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number4 48-4
DOIs
StatePublished - 2000

Keywords

  • Carbachol
  • Epidermal growth factor
  • Mitogen-activated protein kinase
  • Protein kinase C
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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