Epidermal Growth factor potentiates the Transmitter-Induced Stimulation of C-AMP and Inositol Phosphates in Human Pigment Epithelial Cells in Culture

NP Liu, F FitzGibbon, M Nash, NN Osborne

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    17 Citations (Scopus)

    Abstract

    Salbutamol, isoproterenol and dopamine stimulate C-AMP production in human retinal pigment epithelium (RPE) cells by activation of β2-type receptors. Epidermal growth factor (EGF) in contrast does not alter basal levels of C-AMP but elevates in an apparently dose-dependent manner the isoproterenol-induced stimulation of C-AMP. EGF also potentiates the forskolin-induced stimulation of C-AMP but has no effect on the elevation of C-AMP caused by NECA (5′-[N-ethyl]-carboxamido adenosine), an adenosine A2-receptor agonist. EGF, isoproterenol and NECA have no effect on basal levels of inositol phosphates (InsPs) in human RPE cells, but EGF specifically elevates the carbachol-induced stimulation of InsPs. The carbachol effect on InsPs is attenuated by the phorbol ester PMA (4β-phorbol 12 myrisate 13-acetate). PMA did not, however, affect the stimulation of C-AMP caused by isoproterenol. The interaction of EGF and C-AMP is further demonstrated in experiments where the incorporation of [3H]thymidine into RPE cells was studied, as an index for proliferation. EGF stimulates RPE cell proliferation while isoproterenol and dibutyryl C-AMP nullify the EGF effect. Dibutyryl C-AMP has a negative effect on RPE cell proliferation while isoproterenol is ineffective.The data presented here suggest that after stimulation of EGF receptors, tyrosine-kinase-activated products can influence secondary messenger products produced from activation of β2-type (linked with C-AMP formation) and muscarinic (linked with InsPs production) receptors in RPE cells. We could find no evidence of an interaction between receptors associated with C-AMP and InsPs/diacylglycerol production.
    Original languageEnglish
    Pages (from-to)489-497
    JournalExperimental Eye Research
    Volume55
    Issue number3
    DOIs
    Publication statusPublished - Sep 1992

    Keywords

    • Epidermal growth factor
    • C-AMP
    • inositol phosphates
    • pigment epithelial cells

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