title: The globin fragment LVV-hemorphin-7 is an endogenous ligand for the AT4 receptor in the brain.
abstract: Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with specific high-affinity receptors to increase memory retrieval, enhance dopamine-induced stereotypy behavior, and induce c-fos expression in several brain nuclei. We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep brain that binds with high affinity to the angiotensin IV receptor. The peptide was isolated using 125I-angiotensin IV binding to bovine adrenal membranes to assay receptor binding activity. This peptide is identical to the amino acid sequence 30-39 of sheep betaA- and betaB-globins and has previously been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV-hemorphin-7 and angiotensin IV were equipotent in competing for 125I-angiotensin IV binding to sheep cerebellar membranes and displayed full cross-displacement. Using in vitro receptor autoradiography, 125I-LVV-hemorphin-7 binding to sheep brain sections was identical to 125I-angiotensin IV binding in its pattern of distribution and binding specificity. This study reveals the presence of a globin fragment in the sheep brain that exhibits a high affinity for, and displays an identical receptor distribution with, the angiotensin IV receptor. This globin fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the angiotensin IV receptor in the CNS.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Victoria, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Moeller
authors.forename: R A
authors.initials: RA
authors.lastname: Lew
authors.forename: F A
authors.initials: FA
authors.lastname: Mendelsohn
authors.forename: A I
authors.initials: AI
authors.lastname: Smith
authors.forename: M E
authors.initials: ME
authors.lastname: Brennan
authors.forename: T J
authors.initials: TJ
authors.lastname: Tetaz
authors.forename: S Y
authors.initials: SY
authors.lastname: Chai
mesh_terms: D000311:Adrenal Glands / Q000737:chemistry; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D002417:Cattle; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006454:Hemoglobins / Q000302:isolation & purification / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D012756:Sheep
chemical_list: C090830:AT4 receptor; D006454:Hemoglobins; D007457:Iodine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C074309:LVV-hemorphin-7