Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions

J Biol Chem. 2008 Nov 14;283(46):31949-59. doi: 10.1074/jbc.M804784200. Epub 2008 Aug 26.

Abstract

Somatostatin is important in the regulation of diverse neuroendocrine functions. Based on bioinformatic analyses of evolutionarily conserved sequences, we predicted another peptide hormone in pro-somatostatin and named it neuronostatin. Immuno-affinity purification allowed the sequencing of an amidated neuronostatin peptide of 13 residues from porcine tissues. In vivo treatment with neuronostatin induced c-Fos expression in gastrointestinal tissues, anterior pituitary, cerebellum, and hippocampus. In vitro treatment with neuronostatin promoted the migration of cerebellar granule cells and elicited direct depolarizing actions on paraventricular neurons in hypothalamic slices. In a gastric tumor cell line, neuronostatin induced c-Fos expression, stimulated SRE reporter activity, and promoted cell proliferation. Furthermore, intracerebroventricular treatment with neuronostatin increased blood pressure but suppressed food intake and water drinking. Our findings demonstrate diverse neuronal, neuroendocrine, and cardiovascular actions of a somatostatin gene-encoded hormone and provide the basis to investigate the physiological roles of this endogenously produced brain/gut peptide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Pressure / drug effects
  • Cells, Cultured
  • Computational Biology
  • Conserved Sequence
  • Heart / drug effects
  • Humans
  • Mice
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organ Specificity
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Protein Precursors / pharmacology
  • Rats
  • Sequence Alignment
  • Somatostatin / chemistry
  • Somatostatin / genetics
  • Somatostatin / metabolism*
  • Somatostatin / pharmacology
  • Swine

Substances

  • Peptide Fragments
  • Protein Precursors
  • neuronostatin protein, rat
  • Somatostatin