What is the clinical evidence from this study?

Study design: Other. Intervention: [125I]-sar1,ile8-ANG II vs. unlabeled ANG II. Primary outcome: Binding to brain ANG II receptors.

What question did this study set out to answer?

Characterize brain angiotensin II receptor binding properties and map their neuroanatomical distribution along the rostral third ventricle using a radiolabeled antagonist.

April 1, 2008Neuroendocrinology

Localization of Central Angiotensin II Receptors with 125 I-sar 1 , ile 8 -Angiotensin II: Periventricular Sites of the Anterior Third Ventricle

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Key result

Autoradiographic images of [125I]-sar1,ile8-ANG II binding revealed heavy labeling in the lamina terminalis, providing pharmacological evidence for the rostral third ventricle as a site for central ANG II actions.

Population

Brain tissue preparations

Comparison

[125I]-sar1,ile8-ANG II vs Unlabeled antagonist or ANG II

Design

Preclinical

Authors

DHDennis P. HealyBayer (United States)AMAndrzej R. MaciejewskiUniversity of California, San Diego MPMorton P. PrintzUniversity of California, San Diego

Discussion

Member takes

Implication

May inform preclinical models of central ANG II signaling; leaves open relevance to human cardiovascular disease.

Key Points

Characterize brain angiotensin II receptor binding properties and map their neuroanatomical distribution along the rostral third ventricle using a radiolabeled antagonist.
Assessed radioligand binding kinetics in membrane homogenates of the hypothalamus, thalamus, septum, and midbrain (HTSM) using [125I]-sar1,ile8-angiotensin II.
Conducted in vitro autoradiography on brain slices spanning the rostral third ventricle incubated with 0.5 nM [125I]-sar1,ile8-angiotensin II in the presence or absence of 1 µM unlabelled angiotensin II.
Homogenate binding identified a single class of high-affinity sites with a KD of 0.42 ± 0.03 nM, Bmax of 5.98 fmol/mg protein, and Hill slope of 0.84 ± 0.05.
Competition assays showed the unlabeled antagonist bound with higher affinity than native angiotensin II (Ki of 0.22 ± 0.03 nM vs 0.95 ± 0.06 nM, respectively).
Autoradiographic images revealed dense receptor localization in the lamina terminalis, specifically the subfornical organ, median preoptic nucleus, and organum vasculosum laminae terminalis.

Structured PICO

Population

Brain tissue preparations (homogenate preparations of the hypothalamus, thalamus, septum and midbrain, and brain slices from the region of the rostral third ventricle)

Intervention

[125I]-sar1,ile8-ANG II (radiolabeled angiotensin II antagonist)

Comparator

Unlabeled antagonist or ANG II

Outcome

Binding affinity and receptor localizationsurrogate

The study demonstrates the utility of [125I]-sar1,ile8-ANG II for mapping brain ANG II receptors and identifies the rostral third ventricle as a key site for central ANG II actions.

Cite This Study

Healy et al. (2008) studied this question. [125I]-sar1,ile8-ANG II vs. unlabeled ANG II was evaluated on Binding to brain ANG II receptors. Autoradiographic images of [125I]-sar1,ile8-ANG II binding revealed heavy labeling in the lamina terminalis, providing pharmacological evidence for the rostral third ventricle as a site for central ANG II actions.

synapsesocial.com/papers/6a85b30f58b280cb0bc92bba https://doi.org/10.1159/000124615

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Localization of Central Angiotensin II Receptors with 125 I-sar 1 , ile 8 -Angiotensin II: Periventricular Sites of the Anterior Third Ventricle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Localization of Central Angiotensin II Receptors with 125 I-sar 1 , ile 8 -Angiotensin II: Periventricular Sites of the Anterior Third Ventricle

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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