Thrittene, homologous with somatostatin-28((1-13)), is a novel peptide in mammalian gut and circulation.

Published

Journal Article

Preprosomatostatin is a gene expressed ubiquitously among vertebrates, and at least two duplications of this gene have occurred during evolution. Somatostatin-28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin (ProS), are differentially expressed in mammalian neurons, D cells, and enterocytes. One pathway for the generation of S-14 entails the excision of Arg13-Lys14 in S-28, leading to equivalent amounts of S-28((1-12)). Using an antiserum (F-4), directed to the N-terminal region of S-28 that does not react with S-28((1-12)), we detected a peptide, in addition to S-28 and ProS, that was present in human plasma and in the intestinal tract of rats and monkeys. This F-4 reacting peptide was purified from monkey ileum; and its amino acid sequence, molecular mass, and chromatographic characteristics conformed to those of S-28((1-13)), a peptide not described heretofore. When extracts of the small intestine were measured by RIA, there was a discordance in the ratio of peptides reacting with F-4 and those containing the C terminus of ProS, suggesting sites of synthesis for S-28((1-13)) distinct from those for S-14 and S-28. This was supported by immunocytochemistry, wherein F-4 reactivity was localized in gastrointestinal (GI) endocrine cells and a widespread plexus of neurons within the wall of the distal gut while immunoreactivity to C-terminal domains of S-14 and S-28 in these neurons was absent. Further, F-4 immunoreactivity persisted in similar GI endocrine cells and myenteric neurons in mice with a targeted deletion of the preprosomatostatin gene. We believe that these data suggest a novel peptide produced in the mammalian gut, homologous with the 13 residues of the proximal region of S-28 but not derived from the ProS gene. Pending characterization of the gene from which this peptide is derived, its distribution, and function, we have designated this peptide as thrittene. Its localization in both GI endocrine cells and gut neurons suggests that thrittene may function as both a hormone and neurotransmitter.

Full Text

Duke Authors

Cited Authors

  • Ensinck, JW; Baskin, DG; Vahl, TP; Vogel, RE; Laschansky, EC; Francis, BH; Hoffman, RC; Krakover, JD; Stamm, MR; Low, MJ; Rubinstein, M; Otero-Corchon, V; D'Alessio, DA

Published Date

  • July 2002

Published In

Volume / Issue

  • 143 / 7

Start / End Page

  • 2599 - 2609

PubMed ID

  • 12072392

Pubmed Central ID

  • 12072392

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/endo.143.7.8904

Language

  • eng

Conference Location

  • United States