Structure of the precursor for vasoactive intestinal contractor (VIC): its comparison with those of endothelin-1 and endothelin-3.

Vasoactive intestinal contractor (VIC) is a member of the endothelin (ET) peptide family, which evokes a strong contractile response in the ileum, its gene being expressed only in the intestine. Using dot blot analysis, we carried out an interspecies comparison of the nucleotide and deduced amino acid sequences of the precursor for VIC with those of ET-1 and ET-3 to investigate the physiological significance of processing of the precursor for VIC. The highly conserved amino acid sequence was observed between the big form region (big VIC, big ET-1, and big ET-3) of about 40 amino acids and the like peptide region (VIC-like peptide, ET-1-like peptide, and ET-3-like peptide) of 15 amino acids downstream from the big form region. Sequence identity of amino acids of the precursors of ET-1 and ET-3 with that of VIC was 29 and 28%, respectively. Thus, the precursors for the three peptides might have arisen from a common progenitor gene. However, apparent cleavage sites of the like peptide regions are rather unique in the VIC-like peptide, i.e., it had dibasic amino acids at the amino and carboxy termini. Therefore, we suggest that the VIC-like peptide might be liberated from its precursor protein and play some role in the intestine in vivo.