Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor.
We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from many species. The binding site is pharmacologically distinct from the classic angiotensin receptors (AT1 or AT2) displaying low affinity for the known agonists (AII and AIII) and antagonist (Sar1,Ile8-AII). Although a definitive function has not been assigned to this system in many of the tissues in which it resides, AIV's interaction with endothelial cells may involve a role in endothelial cell-dependent vasodilation. Consequent to this action, AIV is a potent stimulator of renal cortical blood flow.
Swanson
G N
GN
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164-6520.
Hanesworth
J M
JM
Sardinia
M F
MF
Coleman
J K
JK
Wright
J W
JW
Hall
K L
KL
Miller-Wing
A V
AV
Stobb
J W
JW
Cook
V I
VI
Harding
E C
EC
D000302:Adrenal Cortex / Q000378:metabolism; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D011869:Radioligand Assay; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects
D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-