A globin fragment, LVV-hemorphin-7, induces [3H]thymidine incorporation in a neuronal cell line via the AT4 receptor

Ingrid Moeller, Anthony L. Albiston, Rebecca A. Lew, Frederick A.O. Mendelsohn, Siew Yeen Chai

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The AT4 receptor was characterized initially as a specific binding site for angiotensin IV, a C-terminal fragment of the vasoactive peptide angiotensin II. Recently, we found that LVV-hemorphin-7, a fragment of β globin, is an abundant peptide in the brain and binds to the AT4 receptor with high affinity and specificity. In the neuroblastoma/glioma hybrid cell line, NG108-15, LVV-hemorphin-7 and angiotensin IV competed for 125I- angiotensin IV binding in a biphasic fashion with IC50 values of 1.2 x 10 m and 1.1 x 10-9 M for the high-affinity site, respectively, and 6.7 x 10- 8 and 1.5 x 10-8 M for the low-affinity site, respectively. Both peptides were internalized rapidly by the cells. However, LVV-hemorphin-7, but not angiotensin IV, elicited a 1.8-fold increase in DNA synthesis in a dose- dependent manner. Furthermore, coincubation of the cells with an excess of angiotensin IV (10-6 M) inhibited LVV-hemorphin-7-stimulated DNA synthesis. Therefore, whereas LVV-hemorphin-7 and angiotensin IV were capable of binding to the AT4 receptor, only LVV-hemorphin-7 elicited [3H]thymidine incorporation in NG108-15 cells, n contrast, angiotensin IV behaved as an antagonist. The current finding suggests that LVV-hemorphin-7 is a functional peptide in the central nervous system and in view of its abundance in neural tissue, compared with angiotensin IV, may be of significant physiological importance.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalJournal of Neurochemistry
Issue number1
Publication statusPublished - 1 Jul 1999
Externally publishedYes


  • [H]Thymidine incorporation
  • Angiotensin IV
  • AT receptors
  • Brain
  • Globin

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