Epidermal growth factor potentiates the transmitter-induced stimulation of C-AMP and inositol phosphates in human pigment epithelial cells in culture.
Salbutamol, isoproterenol and dopamine stimulate C-AMP production in human retinal pigment epithelium (RPE) cells by activation of beta 2-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 (4 beta-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 beta 2-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.
Liu
N P
NP
Nuffield Laboratory of Ophthalmology, Oxford University, U.K.
Fitzgibbon
F
F
Nash
M
M
Osborne
N N
NN
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D013268:Stimulation, Chemical
D007295:Inositol Phosphates; D004815:Epidermal Growth Factor; D004247:DNA; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol; D004298:Dopamine