Discrimination of two angiotensin II receptor subtypes with a selective agonist analogue of angiotensin II, p-aminophenylalanine6 angiotensin II

Biochem Biophys Res Commun. 1990 Jun 29;169(3):997-1006. doi: 10.1016/0006-291x(90)91993-3.

Abstract

Angiotensin II receptor binding sites in rat liver and PC12 cells differ in their affinities for a nonpeptidic antagonist, DuP 753, and p-aminophenylalanine6 angiotensin II. In liver, which primarily contains the sulfhydryl reducing agent-inhibited type of angiotensin II receptor, which we refer to as the AII alpha subtype, DuP 753 displays an IC50 of 55 nM, while p-aminophenylalanine6 angiotensin II displays an IC50 of 8-9 microM. In PC12 cells, which primarily contain the angiotensin II receptor type whose binding affinity is enhanced by sulfhydryl reducing agents (AII beta), DuP 753 displays an IC50 in excess of 100 microM, while p-aminophenylalanine6 angiotensin II displays an IC50 of 12 nM. p-Aminophenylalanine6 angiotensin II binding affinity in liver is decreased in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) suggesting that this analogue is an agonist.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms / metabolism
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / metabolism
  • Animals
  • Binding, Competitive
  • Cell Membrane / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • Imidazoles / metabolism
  • In Vitro Techniques
  • Liver / metabolism
  • Losartan
  • Mercaptoethanol / pharmacology
  • Pheochromocytoma / metabolism
  • Rats
  • Receptors, Angiotensin / classification*
  • Receptors, Angiotensin / metabolism
  • Tetrazoles / metabolism
  • Thionucleotides / pharmacology

Substances

  • Imidazoles
  • Receptors, Angiotensin
  • Tetrazoles
  • Thionucleotides
  • Angiotensin II
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Mercaptoethanol
  • Guanosine Triphosphate
  • angiotensin II, 4-amino-Phe(6)-
  • Losartan