The globin fragment LVV-hemorphin-7 is an endogenous ligand for the AT4 receptor in the brain.
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.
Moeller
I
I
Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Victoria, Australia.
Lew
R A
RA
Mendelsohn
F A
FA
Smith
A I
AI
Brennan
M E
ME
Tetaz
T J
TJ
Chai
S Y
SY
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
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