title: Cellular targets for angiotensin II fragments: pharmacological and molecular evidence.
abstract: Although angiotensin II has long been considered to represent the end product of the renin-angiotensin system (RAS), there is accumulating evidence that it encompasses additional effector peptides with diverse functions. In this respect, angiotensin IV (Ang IV) formed by deletion of the two N terminal amino acids, has sparked great interest because of its wide range of physiological effects. Among those, its facilitatory role in memory acquisition and retrieval is of special therapeutic relevance. High affinity binding sites for this peptide have been denoted as  AT(4)- receptors  and, very recently, they have been proposed to correspond to the membrane-associated OTase/ IRAP aminopeptidase. This offers new opportunities for examining physiological roles of Ang IV in the fields of cognition, cardiovascular and renal metabolism and pathophysiological conditions like diabetes and hypertension. Still new recognition sites may be unveiled for this and other angiotensin fragments. Recognition sites for Ang-(1-7) (deletion of the C terminal amino acid) are still elusive and some of the actions of angiotensin III (deletion of the N terminal amino acid) in the CNS are hard to explain on the basis of their interaction with AT(1)-receptors only. A more thorough cross-talk between in vitro investigations on native and transfected cell lines and in vivo investigations on healthy, diseased and transgenic animals may prove to be essential to further unravel the molecular basis of the physiological actions of these small endogenous angiotensin fragments.
authors.affiliation: Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel (VUB), Sint-Genesius, Rode, B-1640, Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Vauquelin
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Sophie
authors.initials: S
authors.lastname: Sarre
authors.forename: Guy
authors.initials: G
authors.lastname: Ebinger
authors.forename: Alain
authors.initials: A
authors.lastname: Dupont
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanderheyden
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D002477:Cells / Q000378:metabolism; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism
chemical_list: C090830:AT4 receptor; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; D010122:Cystinyl Aminopeptidase; C118790:angiotensin I (1-7)