Thrittene, homologous with somatostatin-28((1-13)), is a novel peptide in mammalian gut and circulation.
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.
Ensinck
John W
JW
Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle 98195, USA.
Baskin
Denis G
DG
Vahl
Torsten P
TP
Vogel
Robin E
RE
Laschansky
Ellen C
EC
Francis
Bruce H
BH
Hoffman
Ross C
RC
Krakover
Jonathan D
JD
Stamm
Michael R
MR
Low
Malcolm J
MJ
Rubinstein
Marcelo
M
Otero-Corchon
Veronica
V
D'Alessio
David A
DA
D000328:Adult; D000818:Animals; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004064:Digestive System / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010446:Peptide Fragments; D011498:Protein Precursors; C460363:thrittene protein, human; D013004:Somatostatin; C028456:prosomatostatin