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A range of N-terminal fragments of substance P (SP) were evaluated for inhibitory activity against angiotensin converting enzyme (ACE) from rat lung and brain (striatum). SP inhibited the enzyme from both sources in a concentration dependent manner (IC50 30 microM). The N-terminal fragments SP[1-7], SP[1-6], SP[1-4] and SP[3-4] were equipotent with SP for both sources of the enzyme. However, SP[1-3] showed a difference in its activity, being more active than SP (IC50 10 microM) in inhibiting the brain enzyme, but inactive against lung ACE. These results suggest that the inhibitory action of SP on ACE resides in the N-terminus of the peptide. The difference in reactivity towards SP[1-3] lends support to the idea that lung and brain ACE are different isozymes. |
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