Effects of epidermal growth factor on signal transduction in rabbit parietal cells.
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+.
Lewis
J J
JJ
Department of Surgery, Yale University School of Medicine, New Haven 06510.
Goldenring
J R
JR
Asher
V A
VA
Modlin
I M
IM
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*
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