Sheep hypothalamus contains a non-angiotensin ligand for type 1 and type 2 angiotensin II receptors.

1. The aim of this study was to determine whether the brain contains an alternative ligand for angiotensin II (AII) receptors. 2. A radioreceptor assay based upon bovine cerebellar membranes (Type 2 AII receptors) was used to monitor the partial purification of an AII-like material from sheep hypothalami. 3. This material displaces 125I-[Sar1, Ala8]-AII from both type 1 (rat adrenal capsular membranes) and Type 2 AII receptors in a manner parallel to that of AII. It has a size of approximately 30,000 Da, is strongly cationic, is stable to boiling but is destroyed by trypsin. It is not recognized by AII antisera. 4. These data provide direct evidence for a non-angiotensin endogenous ligand for brain AII receptors. This novel ligand may play a role in the regulation of blood pressure and other actions mediated by brain AII receptors.