Tyrosine in position 4 is the key amino acid for the binding of angiotensin II to human arteriolar receptor

Endocrinol Jpn. 1987 Oct;34(5):737-43. doi: 10.1507/endocrj1954.34.737.

Abstract

In order to detect the portion of the angiotensin II molecule binding to the human arteriolar receptor, angiotensin II-(1-5)-pentapeptide, angiotensin II-(1-4)-tetrapeptide and angiotensin II-(1-3)-tripeptide were infused intravenously as saline solutions into the same 5 normal men from 0900 h at a rate of 30 nmol (20 micrograms)/kg.min (1.2 ml/min) for 15 minutes, at a rate of 90 nmol (54.5 micrograms)/kg.min (3.0 ml/min) for 6 minutes and at a rate of 140 nmol (54.5 micrograms)/kg.min (3.0 ml/min) for 6 minutes, respectively, on different occasions. At the end of the infusions average increases in blood pressure were 20/22 mmHg (p less than 0.001) and 6/7 mmHg (p less than 0.001), respectively, with the former 2 peptides, while the last peptide showed no pressor action at all. It had previously been found by our research group that angiotensin III, angiotensin II-(3-8)-hexapeptide, angiotensin II-(4-8)-pentapeptide, angiotensin II-(2-7)-hexapeptide, angiotensin II-(1-7)-heptapeptide and angiotensin II-(1-6)-hexapeptide have some pressor action but that angiotensin II-(5-8)-tetrapeptide has no pressor action in normal men. When these previous results are combined with the present result, it is evident that only tyrosine-containing molecules show pressor activity and that tyrosine-deleted molecules do not show pressor activity at all. It is concluded that tyrosine in position 4 is the key amino acid for the binding of angiotensin II to human arteriolar receptor.

Publication types

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

MeSH terms

  • Adult
  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Arterioles / metabolism
  • Blood Pressure / drug effects
  • Humans
  • Male
  • Peptide Fragments / metabolism
  • Receptors, Angiotensin / metabolism*
  • Tyrosine / metabolism*

Substances

  • Peptide Fragments
  • Receptors, Angiotensin
  • Angiotensin II
  • Tyrosine