Journal of medicinal chemistry

Photochemical inactivation of the angiotensin receptor of rabbit aorta by N alpha-(2-nitro-5-azidobenzoyl)-[1-aspartic acid,5-isoleucine]angiotensin II.

PMID 6267278


The photoaffinity label N alpha-(2-nitro-5-azidobenzoyl)-[Asp1,Ile5]angiotensin II (nitroazidobenzoyl-angiotensin II) has a pD2 of 7.22 in the rabbit aortic strip assay compared to 8.44 for [Asp1,Ile5]angiotensin II and can be completely inhibited by [Sar1, Ala8]angiotensin II. Photolysis of a single dose of nitroazidobenzoyl-angiotensin II (0.1 microM) with aortic strips for 3 min with light of wavelengths of greater than 320 nm, followed by washing, resulted in loss of approximately 25% of the strip's response to a subsequent dose of nitroazidobenzoyl-angiotensin II. Photolysis of three consecutive doses of label resulted in loss of 62% of the strips response to a subsequent dose. Repetitive exposure to label in the dark and repetitive photolyses without label resulted in loss of no more than 20% of the strips ability to respond to angiotensin II. Photolysis with three consecutive doses of 0.1 microM nitroazidobenzoyl-angiotensin II in the presence of 0.5 microM of the competitive inhibitor [Sar1,Ala8]angiotensin II decreased the observed inhibition from 62 to 22%. The long-lasting inhibition observed after photolysis with 0.1 microM nitroazidobenzoyl-angiotensin II therefore occurred via photolysis of some part of the nitroazidobenzoyl chromophore. This inhibition was mediated via the receptor that binds [Sar1,Ala8]angiotensin II and, therefore, angiotensin II.