Metabolism of Angiotensin Peptides by Neuronal and Glial Cultures from Rat Brain

The degradation pattern and rate of Ile5]-Angiotensin (Ang) I, II, and III were studied in neuron-enriched and glia-enriched cells in primary cultures from rat brain. Metabolites were separated by HPLC, and their identities were evaluated by comparison of their retention times with those of synthetic Ang peptide fragments and by analysis of their amino acid composition. Major metabolites were identified as des-Asp1-Ile5]-Ang I, des-Asp1-Ile5]-Ang II, Ile5]-Ang II (3-8) hexapeptide, Ile5]-Ang II (4-8) pentapeptide, and Ile5]-Ang II (5-8) tetrapeptide. Glia-enriched cells degraded Ile5]-Ang I and Ile5]-Ang III significantly faster than neuron-enriched cells, whereas no difference between the two types of cells was found in the degradation rate of Ile5]-Ang II. Although the half-lives of Ile5]-Ang I and Ile5]-Ang III in neuron-enriched cells from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were not significantly different, neuron-enriched cultures from WKY rats metabolized Ile5]-Ang II about 2.6 times faster than neuron-enriched cells derived from SHR.