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Functional CRF receptors in BON cells stimulate serotonin release.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2007 Mar 15; Vol. 73 (6), pp. 805-13. Date of Electronic Publication: 2006 Nov 30. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Cell Line, Tumor
Corticotropin-Releasing Hormone pharmacology
Cyclic AMP biosynthesis
Humans
Immunohistochemistry
Peptide Fragments pharmacology
Pyrazoles pharmacology
Receptors, Corticotropin-Releasing Hormone genetics
Triazines pharmacology
Urocortins
Enterochromaffin Cells metabolism
Receptors, Corticotropin-Releasing Hormone physiology
Serotonin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 73
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17184738
- Full Text :
- https://doi.org/10.1016/j.bcp.2006.11.019