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AT4 receptors: specificity and distribution

J W Harding1, J W Wright, G N Swanson

  • 1Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman.

Kidney International
|December 1, 1994
PubMed
Summary
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Radiolabeling of Angiotensin peptides.

Methods in molecular medicine·2011

The AT4 receptor selectively binds Angiotensin (Ang) IV, differing from AT1/AT2 receptors. This novel receptor was identified in various mammalian tissues, including human and monkey, with distinct kidney distribution.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Molecular Biology

Background:

  • The renin-angiotensin system (RAS) involves peptides like Angiotensin (Ang) II, Ang III, and Ang IV.
  • Specific receptors, AT1 and AT2, are known to bind Ang II and Ang III.
  • The existence and function of a distinct receptor for Ang IV, termed AT4, remain to be fully elucidated.

Purpose of the Study:

  • To characterize the AT4 receptor's binding properties.
  • To determine the tissue distribution of AT4 receptors in mammals.
  • To investigate the differential distribution of AT4 receptors compared to AT1/AT2 receptors in the rat kidney.

Main Methods:

  • Radioligand binding assays using bovine adrenal cortex.
  • Competition binding studies with various angiotensin analogs and known AT1/AT2 receptor antagonists.

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  • Tissue screening across multiple mammalian species, including humans and monkeys.
  • Comparative analysis of AT4 and AT1/AT2 receptor distribution in rat kidney sections.

    • Main Results:

    • The AT4 receptor in bovine adrenal cortex exhibited high affinity (Kd = 0.74 ± 0.14 nM) and a specific binding capacity (Bmax = 3.82 ± 1.12 pmol/mg prot).
    • Affinity ranking demonstrated specific binding of Ang IV, with significantly lower affinity for Ang III, d-Arg-Ang II, and minimal binding for Ang II, Sar1,Ile8-Ang II, Ang II (1-7), DuP753, CGP42112A, and PD123177.
    • AT4 receptors were detected in numerous tissues from human and monkey, indicating broad mammalian presence.
    • Differential distribution patterns were observed between AT4 and AT1/AT2 receptors within the rat kidney.

    Conclusions:

    • The AT4 receptor is a distinct entity that specifically binds Angiotensin IV.
    • The widespread presence of AT4 receptors across mammalian species suggests significant physiological roles.
    • The differential localization of AT4 receptors relative to AT1/AT2 receptors in the kidney points to specialized functions within this organ.