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Preliminary biochemical characterization of the novel, non-AT1, non-AT2 angiotensin binding site from the rat brain

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An Erratum to this article was published on 06 May 2010

Abstract

A novel binding site for angiotensins II and III was recently discovered in brain membranes in the presence of the sulfhydryl reactive angiotensinase inhibitor parachloromercuribenzoate. This binding site is distinctly different from the other known receptors for angiotensins: AT1, AT2, AT4, and mas oncogene protein (Ang 1-7 receptor). Preliminary biochemical characterization studies have been done on this protein by crosslinking it with 125I-labeled photoaffinity probes and solubilizing the radiolabeled binding site. Polyacrylamide gel electrophoresis studies and isoelectric focusing indicate that this membrane bound binding site is a protein with a molecular weight of 70–85 kDa and an isoelectric point of ~7. Cyanogen bromide hydrolysis of the protein yielded two radiolabeled fragments of 12.5 and 25 kDa. The protein does not appear to be N-glycosylated based upon the failure of PNGaseF to alter its migration rate on a 7.5% polyacrylamide gel. The binding of angiotensin II to this protein is not affected by GTPγS or Gpp(NH)p, suggesting that it is not a G protein-coupled receptor. Further characterization studies are directed to identify this protein either as a novel angiotensin receptor, an angiotensin scavenger (clearance receptor) or an angiotensinase.

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Acknowledgments

Portions of this work were carried out at the University of Mississippi and were supported by the Peptide Radioiodination Service Center of the University of Mississippi. This work is also supported by NHLBI HL-096357. The authors thank Dr. Kevin Catt for providing the [Sar1,(4-N3)Phe8]-Ang II used in this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University HSC, Amarillo, TX, 79106, USA

    Vardan T. Karamyan

  2. Department of Pharmacology, Université de Sherbrooke, Sherbrooke, QC, Canada

    Jason Arsenault & Emanuel Escher

  3. Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 S. University Dr, Fort Lauderdale, FL, 33328-2018, USA

    Robert C. Speth

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  1. Vardan T. Karamyan
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  2. Jason Arsenault
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  3. Emanuel Escher
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  4. Robert C. Speth
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Correspondence to Robert C. Speth.

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An erratum to this article is available at http://dx.doi.org/10.1007/s12020-010-9347-z.

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Karamyan, V.T., Arsenault, J., Escher, E. et al. Preliminary biochemical characterization of the novel, non-AT1, non-AT2 angiotensin binding site from the rat brain. Endocr 37, 442–448 (2010). https://doi.org/10.1007/s12020-010-9328-2

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  • DOI: https://doi.org/10.1007/s12020-010-9328-2

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