Identification of angiotensin II receptor subtypes

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Abstract

We have demonstrated the existence of two distinct subtypes of the angiotensin II receptor in the rat adrenal gland using radioligand binding and tissue section autoradiography. The identification of the subtypes was made possible by the discovery of two structurally dissimilar, nonpeptide compounds, DuP 753 and EXP655, that show reciprocal selectivity for the two subtypes. In the rat adrenal cortex, DuP 753 inhibited 80% of the total AII binding with an IC50 value on the sensitive sites of 2 × 10−8 M, while EXP655 displaced only 20%. In the rat adrenal medulla, EXP655 gave 90% inhibition of AII binding with an IC50 value of 3.0 × 10−8 M, while DuP 753 was essentially inactive. The combination of the two compounds completely inhibited AII binding in both tissues.

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      Citation Excerpt :

      The NTS as the site of afferent baroreceptor termination in the medulla and the PVN have a significant effect on sympathetic output indirectly through modulation of the neuronal activity of the RVLM area [42]. With the help of highly selective nonpeptide AngII receptor antagonists such as losartan (AT1) and PD123177 (AT2), it has been possible to distinguish between two different AngII receptor subtypes, termed AT1 and AT2 receptors, respectively [43,44]. All AngII effects are mediated by these two receptors [45,46].

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