A globin fragment, LVV-hemorphin-7, induces [H-3]thymidine incorporation in a neuronal cell line via the AT(4) receptor

The AT(4) receptor was characterized initially as a specific binding site f or angiotensin [V, a C-terminal fragment of the vasoactive peptide angioten sin II. Recently, we found that LVV-hemorphin-7, a fragment of beta globin, is an abundant peptide in the brain and binds to the AT(4) receptor with h igh affinity and specificity. In the neuroblastoma/glioma hybrid cell line, NG108-15, LVV-hemorphin-7 and angiotensin IV competed for I-125-angiotensi n IV binding in a biphasic fashion with IC50 values of 1.2 x 10(-10) 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 angio tensin IV, elicited a 1.8-fold increase in DNA synthesis in a dose-dependen t manner. Furthermore, coincubation of the cells with an excess of angioten sin IV (10(-6) M) inhibited LVV-hemorphin-7-stimulated DNA synthesis. There fore, whereas LVV-hemorphin-7 and angiotensin IV were capable of binding to the AT(4) receptor, only LVV-hemorphin-7 elicited [H-3]thymidine incorpora tion in NG108-15 cells, in contrast, angiotensin IV behaved as an antagonis t. The current finding suggests that LVV-hemorphin-7 is a functional peptid e in the central nervous system and in view of its abundance in neural tiss ue, compared with angiotensin IV, may be of significant physiological impor tance.