[Angiotensin IV, a new component of the renin-angiotensin system, which acts on kidney cells]

Angiotensin IV (Ang IV), the hexapeptide obtained from angiotensin II (Ang II) by deletion of the first two N terminal amino acids, possesses specific receptors in various tissues. Our aim was to search for such receptors in two types of renal cells, rat mesangial cells and principal cells of the human collecting duct. [125I]-Ang IV specifically bound to mesangial cell surface and to membranes prepared from the principal cells. In both cases, affinity was approximately 5 nmol/L and receptor density was close to 1000 fmol/mg protein. The order of potency of different competitors was as follows: Ang IV > Ang III > Ang II > Ang II (4-8) > Ang II (1-7). Binding sites were distinct from those of Ang II since type 1 or type 2 Ang II receptor nonpeptide antagonists produced no displacement. Reciprocally, Ang IV did not displace Ang II from its binding sites. Ang IV inhibited the vasoconstrictor effect of Ang II on rat mesangial cells and increases cyclic AMP production in principal cells, but only when it had been previously stimulated. Taken together, these results demonstrate that the glomerulus and the collecting duct represent target sites for Ang IV and suggest that Ang IV could influence the renal functions.