A Specific Binding Site for Angiotensin II(3-8), Angiotensin IV, in Rabbit Cardiac Fibroblasts

Abstract

This study demonstrates the existence of a high affinity binding site on rabbit cardiac fibroblasts of the hexapeptide (3-8) fragment of angiotensin II (AngIV). [125I]-AngIV binding is saturable, reversible and distinct from angiotensin II (AngII) receptors. At 37 degrees C equilibrium of [125I]-AngIV binding is reached within 2 h. AngIV displaces [125I]-AngIV bound to cultured rabbit cardiac fibroblasts whereas AngII receptor-specific ligands ([Sar1, Ile8]-AngII, Dup753, CGP42112A) do not. Scatchard plot analysis revealed that [125I]-AngIV binds to a single class of sites with Kd = 4.87 +/- 0.11 x 10(-9) mol/l, Bmax = 371 +/- 8.3 fmol/mg protein and a Hill coefficient of 0.92. In the presence of the non-hydrolyzable GTP analog GTPgammaS [125I]-AngIV binding in rabbit cardiac fibroblasts was not markedly affected, whereas binding of [125I]-(Sar1,IIe8)-AngII is reduced. The role of AngIV in the heart and in particular in cardiac fibroblasts is unknown, and the putative interaction of AngIV with AngII needs further characterization.

Characterization of the AT4 receptor in a human neuroblastoma cell line (SK‐N‐MC)

“…Ang IV has been previously reported to induce DNA synthesis and cell proliferation in a number of primary cell cultures, including rat anterior pituitary cells (Pawlikowski and Kunert‐Radek 1997), rabbit cardiac fibroblasts (Wang et al . 1995) and bovine coronary microvascular endothelial cells (Hall et al .…”

Angiotensin II: a regulator of cardiomyocyte function and survival

“…In the human myocardium AT 2 expression levels are reported to be at least comparable to AT 1 levels and in some pathological contexts AT 2 is the predominantly expressed subtype (43,44), with fibroblast AT 2 expression particularly pronounced (45). A novel type of angiotensin receptor has also been reported and named the AT 4 receptor (46). This receptor has been identified in cardiac preparations (47), and has been shown to have high affinity for the hexapeptide metabolite of Ang II, commonly known as Angiotensin IV (Ang IV).…”

Angiotensin II and cardiac excitation-contraction coupling: Questions and controversies

“…Selective blockade of the AngII‐induced positive inotropic effect by losartan but not by PD12377 has been observed in cardiac preparations from mammalian species that respond to AngII with potent positive inotropic effects (rabbit and cat), suggesting that AT 1 but not AT 2 is implicated in the AngII‐induced positive inotropic effect 11,41,42 . A novel type of angiotensin receptor has recently been described and named the AT 4 receptor 43 . This receptor has a high affinity for the hexapeptide metabolite of AngII, Ang, 3–8 commonly known as angiotensin IV (AngIV).…”