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A Globin Fragment, LVV‐Hemorphin‐7, Induces [ 3 H]Thymidine Incorporation in a Neuronal Cell Line via the AT 4 Receptor
Author(s) -
Moeller Ingrid,
Albiston Anthony L.,
Lew Rebecca A.,
Mendelsohn Frederick A. O.,
Chai SiewYeen
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730301.x
Subject(s) - angiotensin ii , receptor , angiotensin receptor , peptide , renin–angiotensin system , binding site , thymidine , globin , chemistry , biology , medicine , dna , endocrinology , biochemistry , hemoglobin , blood pressure
The AT 4 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 AT 4 receptor with high affinity and specificity. In the neuroblastoma/glioma hybrid cell line, NG108‐15, LVV‐hemorphin‐7 and angiotensin IV competed for 125 I‐angiotensin IV binding in a biphasic fashion with IC 50 values of 1.2 × 10 ‐10 and 1.1 × 10 ‐9 M for the high‐affinity site, respectively, and 6.7 × 10 ‐8 and 1.5 × 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, co‐incubation 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 AT 4 receptor, only LVV‐hemorphin‐7 elicited [ 3 H]thymidine incorporation in NG108‐15 cells. In 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.