ACTIVATION OF AT(1) ANGIOTENSIN RECEPTORS INDUCES DNA-SYNTHESIS IN A RAT INTESTINAL EPITHELIAL (RIE-1) CELL-LINE

Proliferation of the rat intestinal epithelial cell-line, RIE-1, has p reviously been shown to be stimulated by certain polypeptide growth fa ctors acting via receptors that possess intrinsic tyrosine kinase acti vity. In this study, we show that the octapeptide hormone angiotensin II (AII), apparently acting through the AT(1) G-protein-coupled recept or, is also a mitogen for RIE-1 cells. Maximal stimulation of DNA synt hesis and cellular proliferation occurred at an AII concentration of 1 0-100 nM, with half-maximal stimulation at 1 nM. The mitogenic respons e to AII was completely inhibited by the AT(1) angiotensin-receptor an tagonist, DuP753, but not by the AT(2)-receptor antagonist, PD123319. The early signalling responses activated by AII in RIE-1 cells include increased production of inositol phosphates, a transient increase in the intracellular concentration of free calcium, an activation of prot ein kinase C, and a rapid change in the pattern of cellular protein-ty rosine phosphorylation. These results implicate an activation of the i nositol lipid signalling pathway via the AT(1) receptor subtype in the AII-stimulated mitogenic response of this normal epithelial cell line .