AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 2 460-R465, Copyright © 1993 by American Physiological Society
Evidence for a novel angiotensin II receptor involved in angiogenesis in chick embryo chorioallantoic membrane
F. A. Le Noble, N. H. Schreurs, H. W. van Straaten, D. W. Slaaf, J. F. Smits, H. Rogg and H. A. Struijker-Boudier
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Angiotensin II acts as a growth factor in the cardiovascular system and has
been implicated in angiogenesis. The existence of at least two types of
angiotensin II receptors, the AT1 and the AT2 receptors, has been suggested
by ligand binding studies. We used three different AT receptor antagonists
to study the receptor mediating angiotensin II-induced angiogenesis in the
chorioallantoic membrane (CAM) of the chick embryo. Angiotensin II caused
pronounced angiogenesis of pre- and postcapillary vessels of 30-40%. This
response could only be blocked by adding the peptidergic AT2 antagonist
CGP-42112A. The nonpeptidergic AT2 antagonist PD123319 and AT1 antagonist
losartan (DuP 753) were not effective. In addition, we used radioligand
binding studies with a range of ligands to define the nature of the
receptor. Our results show a high density of specific single class AT
receptor with a total number of binding sites of 1,190 fmol/mg protein and
an affinity constant for angiotensin II of 2.7 nM. The inhibitory
concentrations (IC50) for CGP-42112A, PD 123319 and losartan were 724, >
100,000, and 59,000 nM, respectively. Our studies suggest that these
binding sites act as receptors for angiotensin II-induced angiogenesis.
Both functional and radioligand binding studies suggest that the receptor
is different from the classical mammalian AT1 and AT2 receptors.
