THE GLOBIN FRAGMENT LVV-HEMORPHIN-7 IS AN ENDOGENOUS LIGAND FOR THE AT(4) 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, e nhance dopamine-induced stereotypy behavior, and induce c-fos expressi on in several brain nuclei. We have isolated a decapeptide (Leu-Val-Va l-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep brain that binds with high a ffinity to the angiotensin IV receptor. The peptide was isolated using I-125-angiotensin IV binding to bovine adrenal membranes to assay rec eptor binding activity. This peptide is identical to the amino acid se quence 30-39 of sheep beta(A)- and beta(B)-globins and has previously been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV-hemorphin-7 and angiotensin IV were equipotent in competing for I- 125-angiotensin IV binding to sheep cerebellar membranes and displayed full cross-displacement. Using in vitro receptor autoradiography, I-1 25-LVV-hemorphin-7 binding to sheep brain sections was identical to I- 125-angiotensin IV binding in its pattern of distribution and binding specificity. This study reveals the presence of a globin fragment in t he sheep brain that exhibits a high affinity for, and displays an iden tical receptor distribution with, the angiotensin IV receptor. This gl obin fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the angiotensin IV receptor in the CNS.