Evidence for the existence of a family of biologically active angiotensin I-like peptides in the dog central nervous system.

Husain, Ahsan; Bumpus, F. M.; Smeby, Robert R.; Brosnihan, K. Bridget; Khosla, M. C.; Speth, Robert C.; Ferrario, Carlos M.

doi:10.1161/01.res.52.4.460

Cited by 16 publications

(12 citation statements)

References 25 publications

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“…Contrary to the findings of Husain et al (1983), we found only one N-terminal dog CSF Aogen structure. Husain et al (1983) presented evidence that a family of biologically active Ang I-like peptides were generated when dog CSF was digested with dog kidney renin; 40% of the Ang I-like material was estimated to be a peptide of higher molecular weight rather than [Ile'l-Ang I. Husain et al (1983) concluded the highmolecular-weight peptides were N-terminally modified and speculated that brain and liver elaborated different forms of Aogen.…”

Section: Discussioncontrasting

confidence: 99%

Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Moffett

1987

Journal of Neurochemistry

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Angiotensinogen (Aogen) (CA 11002-13-14), the prohormone of the neuro- and vasoactive peptide angiotensin II (Ang II) (CA 11128-99-7), is found in dog brain as well as in dog plasma. At 2-4 micrograms/ml CSF, Aogen comprises 1-2% of the total protein in dog CSF. Immunopurified CSF and plasma Aogen were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and anion-exchange HPLC. Two major (alpha- and beta-) forms and one minor (gamma-) form of Aogen were observed in dog plasma. The majority of Aogen in dog CSF was chromatographically identical to the gamma-form of plasma Aogen; alpha- and beta-Aogen forms comprised less than 5% of the total CSF Aogen. The N-terminal amino acid sequences of alpha-, beta-, and gamma-Aogen identified these proteins as members of the Aogen family. The N-terminal amino acid sequence of CSF gamma-Aogen was Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-Leu-Leu-Val-Tyr-Ser-Lys-Ser-Ser-(X)-Glu- . More basic than either alpha- or beta-Aogen, gamma-Aogen was shown to be a glycoprotein with an apparent molecular weight (Mr) of 58,000. CSF [des Ang I]-Aogen exhibited a greater anion-exchange HPLC retention. CSF, however, contained only minor amounts of [des Ang I]-Aogen. These analyses have demonstrated that brain overwhelmingly releases one particular Aogen into the CSF; however, very little of this brain Aogen is utilized for the production of Ang I.

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Section: Discussioncontrasting

confidence: 99%

Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Moffett

1987

Journal of Neurochemistry

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“…The discovery of this extended form of Ang I raised our interest since we had previously reported the existence of a family of extended Ang I peptides in the dog’s cerebrospinal fluid [53]. In a series of correlative studies we showed increased expression and content of Ang-(1-12) in the left ventricle of SHR compared with WKY [54].…”

Section: Novel Pathways Upstream From Angiotensin I –The New Research–mentioning

confidence: 99%

An evolving story of angiotensin-II-forming pathways in rodents and humans

et al. 2013

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Lessons learned from the characterization of the biological roles of angiotensin-(1-7) in opposing the vasoconstrictor, proliferative, and prothrombotic actions of angiotensin II created an underpinning for a more comprehensive exploration of the multiple pathways by which the blood and tissues renin angiotensin system regulates homeostasis and its altered state in disease processes. This review summarizes the progress that has been made in the novel exploration of intermediate shorter forms of angiotensinogen through the characterization of the expression and functions of the dodecapeptide angiotensin-(1-12) in the cardiac production of angiotensin II. The studies reveal significant differences in humans versus rodents regarding the enzymatic pathway by which angiotensin-(1-12) undergoes metabolism. Highlights of the research include the demonstration of chymase-direct formation of angiotensin II from angiotensin-(1-12) in human left atrial myocytes and left ventricular tissue, the presence of robust expression of angiotensin-(1-12) and chymase in the atrial appendage of subjects with resistant atrial fibrillation, and the preliminary observation of significantly higher angiotensin-(1-12) expression in human left atrial appendages.

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“…Of these various lines of evidence, the biochemical findings argue strongly but not conclusively for the existence of an extrarenal isorenin angiotensin system in the brain of mammals, including humans. In this respect, the observations that: 1) brain angiotensinogen shows molecular heterogeneity with respect to the plasma counterpart; 37 2) in the dog, the immunochemical characteristics of the isorenin enzyme are distinct from the enzyme of kidney origin; 3 *-" and 3) extended molecular forms of AI can be formed in the CSF 84 are decisive, but not yet conclusive, steps toward proving the existence of a biosynthetic pathway for the formation of angiotensin peptides in the CNS.…”

Section: Framework To Evaluate Future Researchmentioning

confidence: 99%