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S. K. Sharma, C. Austin, A. Howard, G. Lo, C. G. Nicholl, and S. Legon


Gastric inhibitory peptide (GIP) is a 42 amino acid gastrointestinal peptide which inhibits gastric acid secretion and stimulates pancreatic insulin secretion in the presence of glucose. Here we report the sequence of the cDNA encoding the rat GIP precursor. PreproGIP was 144 amino acids in length and comprised the GIP peptide itself, N- and C-terminal flanking peptides of 22 and 59 amino acids respectively and a typical hydrophobic signal peptide. The sequence indicated that GIP is released from its precursor by cleavage at single arginine residues. The C-terminal flanking peptide may have an important function since it was well conserved and contained a region of 16 amino acids with only a single, conservative replacement. Rat GIP mRNA was found in the duodenum and jejunum. Levels of GIP mRNA in the duodenum were increased twofold after a period of 2 days of starvation. There was no detectable expression of the GIP gene in other parts of the gastrointestinal tract or in other endocrine tissues. However, in pancreatic mRNA preparations, a larger mRNA was detected after low stringency hybridization. This could represent a further member of this gene family.

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C Austin, G Lo, K A Nandha, L Meleagros, and S R Bloom


Many peptide precursors encode more than one bioactive peptide. Recent cloning of the rat neuromedin U (NmU) precursor revealed potential proteolytic processing sites which may generate three associated peptides in addition to the NmU peptide, which is known to have potent uterine contractile effects. To assess the degree of evolutionary conservation, which often suggests conserved biological function and hence physiological importance, we have cloned and sequenced the cDNA encoding the human NmU precursor. Sequence analysis revealed a 174 amino acid human precursor containing the 25 residue NmU peptide near the C terminus of the precursor. The human message sequence was 74% homologous with that of the rat, indicating evolutionary conservation of the precursor between these two species. Four out of five of the putative proteolytic processing sites, first revealed in the rat precursor, were conserved in the human precursor, indicating a similar processing mechanism in both species. Two such processing sites flank a 33 residue peptide sequence which differed in only two amino acids compared with the rat homologue. This conservation suggests a possible biological role for this putative peptide.

Northern blot analysis of human gastrointestinal tissues revealed a similar level of mRNA throughout the gastrointestinal tract. RIA using a porcine specific assay showed the highest levels of peptide in the jejunum samples.

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C Austin, M Oka, K A Nandha, S Legon, N Khandan-Nia, G Lo, and S R Bloom


This study has quantified, for the first time, the relative levels of neuromedin U (NmU) mRNA in the rat gastrointestinal tract using Northern blot analysis. NmU message was detected in all regions of the gastrointestinal tract from the oesophagus to the rectum. The greatest levels were found in the duodenum and jejunum, the principal sites for absorption, which were 2·5- and 3-fold respectively above ileal levels.

Quantification of NmU mRNA and peptide contents in the duodenum, jejunum and ileum during postnatal development of the rat showed message and peptide levels to be greater in the maturing rat than in neonates. Message levels in the duodenum, jejunum and ileum showed 14-, 7- and 4-fold increases respectively between 1 and 56 days after birth, whilst the corresponding peptide levels in the duodenum, jejunum and ileum showed 33-, 14- and 25-fold increases respectively.

Food deprivation caused a small, but significant, decrease in message levels in the jejunum and colon, but there was no change in the duodenum or ileum. This shows that the presence of food has little effect on NmU mRNA levels in the gut.