Characterization of the brain-specific non-AT1, non-AT2 angiotensin binding site in the mouse

Karamyan, Vardan T.; Gembardt, Florian; Rabey, Felicia M.; Walther, Thomas; Speth, Robert C.

doi:10.1016/j.ejphar.2008.05.035

Cited by 23 publications

(41 citation statements)

References 50 publications

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“…Separate photoradiolabeling (in the absence of PCMB) and radioligand binding assays indicated that AT 1 and AT 2 receptors were still present in the neurolysin knock-out mouse brains, endorsing earlier observations distinguishing this novel binding site from classic Ang II receptors (16).…”

Section: Discussionsupporting

confidence: 64%

“…Many features of this protein (high affinity and pharmacological specificity for angiotensins; conservation in brains of numerous species, including humans; localization on the plasma membrane, where it can interact with extracellular ligands; and association of expression of this protein with neuronal cell death and neurogenic hypertension) strongly favor its functional significance (16,20). However, the unknown identity of the novel angiotensin binding site has limited our understanding of the (patho)physiological function of this hypothesized new member of the RAS.…”

Section: Discussionmentioning

confidence: 99%

“…The recently discovered non-AT 1 , non-AT 2 angiotensin binding site in rodent and human brain membranes has dis- tinctly different biochemical properties and tissue distribution from classic angiotensin receptors and key angiotensin-processing enzymes (15)(16)(17)(18)(19). Many features of this protein (high affinity and pharmacological specificity for angiotensins; conservation in brains of numerous species, including humans; localization on the plasma membrane, where it can interact with extracellular ligands; and association of expression of this protein with neuronal cell death and neurogenic hypertension) strongly favor its functional significance (16,20).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, in the course of radioligand receptor binding studies of brain angiotensin receptors, we discovered a novel, non-AT 1 , non-AT 2 angiotensin binding site in rat brain membranes (15), which was also confirmed in mouse and human brain membranes (16,17). The non-AT 1 , non-AT 2 binding site has nanomolar affinity and high specificity for angiotensins I, II, and III and is pharmacologically, biochemically, and anatomically different from classical angiotensin type 1 (AT 1 ) and type 2 (AT 2 ) receptors, G-protein coupled Mas receptor, and neprilysin (EC 3.4.24.11, also known as neutral endopeptidase), a protease involved in the processing of angiotensins (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

“…The non-AT 1 , non-AT 2 binding site has nanomolar affinity and high specificity for angiotensins I, II, and III and is pharmacologically, biochemically, and anatomically different from classical angiotensin type 1 (AT 1 ) and type 2 (AT 2 ) receptors, G-protein coupled Mas receptor, and neprilysin (EC 3.4.24.11, also known as neutral endopeptidase), a protease involved in the processing of angiotensins (15)(16)(17)(18)(19). Increased expression of the novel binding site was strongly associated with neuronal cell death following oxidative stress (20), whereas it is reduced in spontaneously hypertensive rat brains (21).…”

mentioning

confidence: 99%

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Identification of Membrane-bound Variant of Metalloendopeptidase Neurolysin (EC 3.4.24.16) as the Non-angiotensin Type 1 (Non-AT1), Non-AT2 Angiotensin Binding Site

Wangler

Santos

Schadock

et al. 2012

Journal of Biological Chemistry

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Background: Angiotensin II, the renin-angiotensin system effector peptide, interacts with a recently discovered binding site that is distinctly different from its classic receptors. Results: A radioiodinated angiotensin II photoprobe bound to a ϳ75-kDa membrane protein, enabling its isolation and identification. Conclusion: Membrane-bound metalloendopeptidase neurolysin (EC 3.4.24.16) is the novel angiotensin-binding protein.Significance: This metalloendopeptidase may be a crucial component of the renin-angiotensin system.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of Membrane-bound Variant of Metalloendopeptidase Neurolysin (EC 3.4.24.16) as the Non-angiotensin Type 1 (Non-AT1), Non-AT2 Angiotensin Binding Site

Wangler

Santos

Schadock

et al. 2012

Journal of Biological Chemistry

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Novel Aspects of the Cardiac Renin–Angiotensin System

Singh

Baker

Kumar

2009

The Local Cardiac Renin-Angiotensin Aldosterone System

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

Karamyan

Arsenault

Escher

et al. 2010

Endocr

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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: AT 1 , AT 2 , AT 4 , and mas oncogene protein (Ang 1-7 receptor). Preliminary biochemical characterization studies have been done on this protein by crosslinking it with 125 I-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 Nglycosylated 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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Characterization of the brain-specific non-AT1, non-AT2 angiotensin binding site in the mouse

Cited by 23 publications

References 50 publications

Identification of Membrane-bound Variant of Metalloendopeptidase Neurolysin (EC 3.4.24.16) as the Non-angiotensin Type 1 (Non-AT1), Non-AT2 Angiotensin Binding Site

Identification of Membrane-bound Variant of Metalloendopeptidase Neurolysin (EC 3.4.24.16) as the Non-angiotensin Type 1 (Non-AT1), Non-AT2 Angiotensin Binding Site

Novel Aspects of the Cardiac Renin–Angiotensin System

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

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