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

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.