title: Effects of epidermal growth factor on signal transduction in rabbit parietal cells.
abstract: The aim of this study was to elucidate the cellular mechanisms of action of epidermal growth factor (EGF) inhibition of parietal cell secretion. EGF effects on histamine- and carbachol-stimulated [14C]aminopyrine (AP) uptake and intrinsic factor (IF) secretion were evaluated in isolated rabbit parietal cells. EGF inhibited histamine-stimulated [14C]AP uptake and IF secretion through a reduction in stimulated adenosine 3',5'-cyclic monophosphate (cAMP) levels. EGF decreased the phosphorylation of a cytosolic 30-kDa, histamine-stimulated, cAMP-dependent protein kinase substrate. These effects on histamine-stimulated activation were reversed by pertussis toxin preincubation. EGF inhibited carbachol-stimulated [14C]AP uptake and IF secretion, but did not alter the carbachol-stimulated Ca2+ transient. These results indicate that EGF inhibits histamine-stimulated secretion through the inhibitory Gi guanosine 5'-triphosphate-binding protein and carbachol-stimulated secretion through a mechanism independent of the activation of an increase in intracellular Ca2+.
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven 06510.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lewis
authors.forename: J R
authors.initials: JR
authors.lastname: Goldenring
authors.forename: V A
authors.initials: VA
authors.lastname: Asher
authors.forename: I M
authors.initials: IM
authors.lastname: Modlin
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001572:Benzofurans; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002217:Carbachol; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007437:Intrinsic Factor / Q000378:metabolism; D007700:Kinetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D002021:Buffers; D005456:Fluorescent Dyes; D011506:Proteins; D000632:Aminopyrine; C049925:fura-2-am; D005576:Colforsin; D004815:Epidermal Growth Factor; D006632:Histamine; D002217:Carbachol; D007437:Intrinsic Factor; D000242:Cyclic AMP; D002118:Calcium; D016257:Fura-2