ENHANCED EXPRESSION OF NEUROTENSIN NEUROMEDIN-N MESSENGER-RNA AND PRODUCTS OF NT NMN PRECURSOR PROCESSING IN NEONATAL RATS

Intestinal levels of immunoreactive neurotensin (iNT) and neuromedin N (iNMN), as well as mRNA for the NT/NMN precursor, were elevated durin g the suckling period in rats. While transient expression of NT/NMN wa s observed at 1-5 days of age in the proximal small intestine and colo n, NT/NMN levels in the ileum increased to peak at 10-20 days of age a nd then decreased to adult levels. The levels of these peptides were n ot elevated in the central nervous system and pituitary over this time period. Chromatographic analyses of jejunoileal extracts indicated th at large molecular forms of iNT and iNMN were present, constituting ap proximately 1.3% of total iNT and approximately 56% of total iNMN, res pectively. Treatment of the large forms with pepsin, which is known to generate the fully immunoreactive peptides, NT(3-13), NT(4-13), and N MN, increased immunoreactivity tenfold (iNT) and 1.2-fold (iNMN). Thus , large forms actually constituted approximately 13% (iNT) and approxi mately 60% (iNMN). Based upon its physicochemical properties, large mo lecular iNMN was tentatively identified as a 125 residue peptide with NMN at its C-terminus [i.e., rat prepro-NT/NMN(23-147)]. The propertie s of large molecular iNT were most similar to those predicted for the entire precursor [i.e., rat prepro-NT/NMN(23-169)]. These results indi cate a) that enhanced expression of NT/NMN occurs in a tissue-specific manner in rats during the suckling period; b) that the pattern of pre cursor processing in intestine yields primarily NT and a large molecul ar form of NMN.