Phorbol ester-, but not ligand-mediated activation of protein kinase C increases angiotensin binding to rat intestinal epithelial (RIE-1) cells.
Whereas direct activation of protein kinase C (PKC) by the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) increased the subsequent binding of 125I-labelled angiotensin II (125I-AII; 0.5 nM) to RIE-1 cells, ligand-mediated activation of the kinase via angiotensin II (AII), which activates the phosphoinositide (PI) pathway in these cells, had no effect. The apparent inability of AII to increase 125I-AII binding is unlikely to result from simultaneous, but opposing actions of AII on angiotensin receptor number and affinity since the peptide also had no effect on the saturation binding of 125I-AII (10 nM) to the cells. Since 125I-AII binding was unaffected both by AII pretreatment in PKC-depleted cells, and by the calcium ionophore, ionomycin, in PKC-replete cells, an attenuating action of AII (opposing any PKC-mediated increase) on 125I-AII binding mediated via the calcium limb of the PI pathway is also unlikely. Instead, the contrasting effects of AII and TPA on 125I-AII binding to RIE-1 cells appear to relate to the degree of PKC activation elicited by each agent.
Smith
R D
RD
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK.
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008024:Ligands; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate