Functional CRF receptors in BON cells stimulate serotonin release

Biochem Pharmacol. 2007 Mar 15;73(6):805-13. doi: 10.1016/j.bcp.2006.11.019. Epub 2006 Nov 30.


BON cells are human, pancreatic carcinoid-derived, endocrine-like cells that share functional similarities with intestinal enterochromaffin (EC) cells. We investigated the presence of corticotropin-releasing factor (CRF) receptors, their signalling pathways and the functional effects of their stimulation in BON cells (clone #7). Expression analysis showed that BON cells contain mRNA for the CRF receptor types 1 and 2 (CRF1/2), although CRF2 mRNA levels were 23-fold higher than those of CRF1 mRNA. The CRF1/2 ligand, rat/human (r/h)CRF (EC50 = 233 nM), and the selective CRF2 ligand, human urocortin 3 (Ucn 3) (EC50 = 48 nM), induced a dose-dependent increase in cAMP formation. Effects of r/hCRF were blocked by 44% with the selective CRF1 antagonist DMP-696, while the selective CRF2 antagonist antisauvagine-30 had only marginal effects. Both ligands (100 nM) stimulated the release of serotonin with similar efficacy (3-fold increase over basal). Effects of r/hCRF, but not Ucn 3, were blocked by pre-incubation with antisauvagine-30. These observations demonstrate that the EC cell-related BON cells express functional CRF2 receptors linked to the release of serotonin. This suggests that EC cells may be a target for CRF and/or Ucn 3 in the intestine during stress-related responses. Actions of CRF/Ucn 3 and EC cell-derived mediators, such as serotonin, might underlie several motor, secretory and/or sensory disorders of the gastrointestinal (GI) tract which may play a role in the pathophysiology of functional GI disorders, such as irritable bowel syndrome.

MeSH terms

  • Cell Line, Tumor
  • Corticotropin-Releasing Hormone / pharmacology
  • Cyclic AMP / biosynthesis
  • Enterochromaffin Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • Peptide Fragments / pharmacology
  • Pyrazoles / pharmacology
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / physiology*
  • Serotonin / metabolism*
  • Triazines / pharmacology
  • Urocortins


  • DMP 696
  • Peptide Fragments
  • Pyrazoles
  • Receptors, Corticotropin-Releasing Hormone
  • Triazines
  • UCN3 protein, human
  • Urocortins
  • antisauvagine 30
  • Serotonin
  • Corticotropin-Releasing Hormone
  • Cyclic AMP