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Localization of Central Angiotensin II Receptors with [125I]-sar1, ile8-Angiotensin II: Periventricular Sites of the Anterior Third Ventricle

Localization of Central Angiotensin II Receptors with [125I]-sar1, ile8-Angiotensin II:... The radiolabeled angiotensin II (ANG II) antagonist, [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II, was used to study brain ANG II receptors by both homogenate binding and in vitro autoradiography. In homogenate preparations of the hypothalamus, thalamus, septum and midbrain (HTSM), [<sup>125</sup>I]-sar<sup>1</sup> ile<sup>8</sup>-ANG II bound to a single class (Hill slope 0.84 ± 0.05) of high affinity binding sites (K<sub>D</sub> 0.42 ± 0.03 nM, B<sub>max</sub> 5.98 ± fmol/mg protein). Competition for the [<sup>125</sup>I]-sar<sup>1</sup> ile<sup>8</sup>-ANG II binding site in HTSM membranes demonstrated a rank order potency characteristic of binding to the ANG II receptor, with the unlabeled antagonist being slightly more potent than ANG II (Ki 0.22 ± 0.03 vs. 0.95 ± 0.06 nM, respectively). Brain slices from the region of the rostral third ventricle were incubated with 0.5 nM [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II in the presence or absence of 1 µM ANG II and exposed to LKB Ultrofilm. Autoradiographic images of [<sup>125</sup>I]-sar’, ile<sup>8</sup>-ANG II binding revealed that structures situated within the anterior wall of the third ventricle, i.e. the lamina terminalis, were heavily labeled; including the subfornical organ, median preoptic nucleus and organum vasculosum laminae terminalis. These results show the utility of [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II as a probe to study brain ANG II receptors and provides pharmacological evidence for the rostral third ventricle as a possible site for central ANG II actions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuroendocrinology Karger

Localization of Central Angiotensin II Receptors with [125I]-sar1, ile8-Angiotensin II: Periventricular Sites of the Anterior Third Ventricle

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Publisher
Karger
Copyright
© 1986 S. Karger AG, Basel
ISSN
0028-3835
eISSN
1423-0194
DOI
10.1159/000124615
Publisher site
See Article on Publisher Site

Abstract

The radiolabeled angiotensin II (ANG II) antagonist, [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II, was used to study brain ANG II receptors by both homogenate binding and in vitro autoradiography. In homogenate preparations of the hypothalamus, thalamus, septum and midbrain (HTSM), [<sup>125</sup>I]-sar<sup>1</sup> ile<sup>8</sup>-ANG II bound to a single class (Hill slope 0.84 ± 0.05) of high affinity binding sites (K<sub>D</sub> 0.42 ± 0.03 nM, B<sub>max</sub> 5.98 ± fmol/mg protein). Competition for the [<sup>125</sup>I]-sar<sup>1</sup> ile<sup>8</sup>-ANG II binding site in HTSM membranes demonstrated a rank order potency characteristic of binding to the ANG II receptor, with the unlabeled antagonist being slightly more potent than ANG II (Ki 0.22 ± 0.03 vs. 0.95 ± 0.06 nM, respectively). Brain slices from the region of the rostral third ventricle were incubated with 0.5 nM [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II in the presence or absence of 1 µM ANG II and exposed to LKB Ultrofilm. Autoradiographic images of [<sup>125</sup>I]-sar’, ile<sup>8</sup>-ANG II binding revealed that structures situated within the anterior wall of the third ventricle, i.e. the lamina terminalis, were heavily labeled; including the subfornical organ, median preoptic nucleus and organum vasculosum laminae terminalis. These results show the utility of [<sup>125</sup>I]-sar<sup>1</sup>, ile<sup>8</sup>-ANG II as a probe to study brain ANG II receptors and provides pharmacological evidence for the rostral third ventricle as a possible site for central ANG II actions.

Journal

Neuroendocrinology – Karger

Published: Jan 1, 1986

Keywords: Organum vasculosum lamina terminalis; Autoradiography; Subfornical organ; Median preoptic nucleus; Sar 1 ile 8 ngiotensin II; Angiotensin II

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