We isolated the human C-type natriuretic peptide gene and identified the peptide in the brain. The human C-type natriuretic peptide gene appeared to be composed of at least two exons and one intron. In the 5′-flanking region, there is an array of cis elements (an inverted CCA AT box, two GC boxes, and a cyclic AMP response element-like sequence) that is not present in upstream sequences of the atrial and brain natriuretic peptide genes. Analysis of the deduced amino acid sequence revealed that human prepro C-type natriuretic peptide comprises 126 amino acids and that the C-terminal 22-residue peptide (G-L-S-K-G-C-F-G-L-K-L-D-R-I-G-S-M-S-G-L-G-C) preceded by Lys-Lys is identical to the porcine counterpart. However, replacement of two amino acids took place in the C-terminal 53-residue sequence, corresponding to another endogenous form of the peptide. Reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay for C-type natriuretic peptide demonstrated that it occurs in the human brain. C-type natriuretic peptide–like immunoreactivity was detected in discrete regions of the human brain, and its level was 10-fold higher than the atrial and brain natriuretic peptide levels, raising the possibility that C-type natriuretic peptide is the major natriuretic peptide in the human brain.
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