HAEMORPHIN PEPTIDES MAY BE ENDOGENOUS LIGANDS FOR BRAIN ANGIOTENSIN AT(4) RECEPTORS

1. Angiotensin IV (AngIV), the (3-8) fragment of AngII, was previously believed to be an inactive metabolite, However, specific binding site s, termed AT(4) receptors, have been identified in the brain and perip heral organs and the peptide has been reported to enhance memory recal l in passive avoidance studies and to dilate pial and renal cortical v essels. 2. AT(4) receptors are distinct from AngII AT(1) and AT(2) rec eptors with respect to function, Ligand specificity and distribution. 3. In the brain, AT(4) receptors are abundant in cerebral and cerebell ar cortex, hippocampal formation and cholinergic systems, as well as s ensory and motor systems. However the peptide AngIV is low or undetect able in the central nervous system. This led us to search for an alter native peptide ligand of the AT(4) receptor. 4. The decapeptide LVVYPW TQRF was isolated from cerebral cortex and binds with high affinity to brain AT4 receptors, This peptide sequence corresponds to an internal sequence of beta-globin and has previously been named LVV-haemorphin 7. 5. Haemorphin may represent a new class of endogenous neuropeptides , some of which interact potently with the brain AT(4) receptor to eli cit a range of actions.