Angiotensin II binding to mammalian brain membranes

J. P. Bennett, S. H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

High affinity binding sites for angiotensin II in bovine and rat brain membranes have been identified and characterized using monoiodinated Ile5 angiotensin II of high specific radioactivity. Degradation of labeled and unlabeled peptide by washed brain particulate fractions was prevented by adding glucagon to the final incubation medium and including a proteolytic enzyme inhibitor (phenylmethylsulfonyl fluoride) in preincubation and incubation procedures. 125I Angiotensin II binding can be studied using either centrifugation or filtration techniques to separate tissue bound radioactivity. 125I Angiotensin II binding to calf brain membranes is saturable and reversible, with a dissociation binding constant of 0.2 nm at 37°. A similar binding constant is found in rat brain membranes. Analogues and fragments of angiotensin II compete for these brain binding sites with potencies which correlate with both their in vivo potencies and their binding inhibition potencies at adrenal cortex angiotensin II receptors. Angiotensin I is 1 to 2 orders of magnitude weaker than angiotensin II; the 3-8 hexapeptide and 4-8 pentapeptide are much weaker still. (des Asp1) angiotensin II (angiotensin III) is slightly more potent than angiotensin II, as are several antagonists of angiotensin II with aliphatic amino acids substituted at position 8. In calf brain 125I angiotensin II binding is restricted almost exclusively to the cerebellum (cortex and deep nuclei). In rat brain, angiotensin II binding is highest in the thalamus hypothalamus, midbrain, and brainstem, areas which are believed to be involved in mediating angiotensin II induced central effects. These findings illustrate the presence of high affinity specific binding sites for antiotensin II in rat and bovine brain and suggest a physiological role for angiotensin peptides in the central nervous system.

Original languageEnglish (US)
Pages (from-to)7423-7430
Number of pages8
JournalJournal of Biological Chemistry
Volume251
Issue number23
StatePublished - 1976

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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