Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C.
Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP gamma s or AIF4- and is inhibited by GDP beta s or pertussis toxin. Alterations in extracellular Ca2+ have no effect on either basal or EGF-stimulated IP3 production. Similarly, treatment with EGTA which decreases cytosolic Ca2+ is without effect. In contrast, treatment with ionomycin which increases cytosolic Ca2+ has no effect on basal IP3 production but enhances the response to EGF. Activation of protein kinase C inhibits IP3 production in response to either EGF or AIF4-. These studies demonstrate the occurrence of EGF-stimulated phospholipase C activity in the rat inner medullary collecting duct. Stimulation by EGF is transduced by a pertussis toxin-sensitive G protein, unaffected by alterations in extracellular Ca2+, insensitive to a decrement in cytosolic Ca2+, enhanced by an increase in cytosolic Ca2+, and inhibited by protein kinase C.
Teitelbaum
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I
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Strasheim
A
A
Berl
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006868:Hydrolysis; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D010738:Type C Phospholipases / Q000502:physiology
D010716:Phosphatidylinositols; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium