Discrimination of two angiotensin II receptor subtypes with a selective agonist analogue of angiotensin II, p-aminophenylalanine6 angiotensin II.
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.
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164.
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D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D019808:Losartan; D008623:Mercaptoethanol / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000145:classification* / Q000378:metabolism; D013777:Tetrazoles / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D013873:Thionucleotides; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008623:Mercaptoethanol; D006160:Guanosine Triphosphate; C064745:angiotensin II, 4-amino-Phe(6)-; D019808:Losartan