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Effects of Urocortins on Intestinal Ion Secretion in the Mouse Colon
Author(s) -
Liu Sumei,
Karo Aaron
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.756.1
Subject(s) - urocortin , receptor , secretion , medicine , ussing chamber , endocrinology , antagonist , chemistry , pharmacology
Background and Aims Urocortins (Ucn1, Ucn2, and Ucn3) belong to the corticotropin‐releasing factor (CRF)‐like peptide family and bind to two subtypes of CRF receptors (CRF 1 and CRF 2 ) to exert their biological effects. Ucn1 binds to both CRF 1 and CRF 2 receptors with equal high affinity, whereas Ucn2 and Ucn3 bind exclusively to CRF 2 . CRF and urocortins are expressed in the gastrointestinal tract. CRF has been implicated in stress‐stimulated intestinal ion secretion and diarrhea. However, the effects of urocortins on intestinal ion secretion have remain uninvestigated. The aim of the present study was to investigate the role of urocortins in the regulation of intestinal ion secretion. Methods Mucosa/submucosa preparations from mouse colon were mounted in Ussing flux chambers for measurement of short‐circuit current ( I sc ) as an indicator of mucosal ion secretion. Results Application of CRF, Ucn1, Ucn2, and Ucn3 to the basolateral side of the preparation increased baseline I sc in a concentration‐dependent manner with an EC 50 (in M) of 1.28×10 −6 , 6.04×10 −7 , 2.89×10 −7 , or 2.98×10 −7 , respectively, with the rank order of potency: Ucn2≈Ucn3>Ucn1>CRF. At 1 μM, Ucn3 caused a greater rise in I sc (Δ I sc : 47.01±8.94 μA/cm 2 ), compared with Ucn2 (17.71±2.63 μA/cm 2 ), Ucn1 (7.06±4.33 μA/cm 2 ), or CRF (8.92±4.11 μA/cm 2 ). The CRF 1 receptor antagonist NBI 27914 significantly suppressed Ucn1‐evoked Δ I sc , but had no effect on Ucn2‐ or Ucn3‐evoked Δ I sc . The CRF 2 receptor antagonist antisauvagine‐30 significantly suppressed Ucn1‐evoked Δ I sc , and completely blocked Ucn2‐ or Ucn3‐evoked Δ I sc . The neuronal blocker tetrodotoxin had no effect on Ucn1‐, Ucn2‐, or Ucn3‐evoked D I sc . Conclusions The results suggest that urocortins stimulate colonic ion secretion independent the submucosal plexus of the enteric nervous system. Both CRF 1 and CRF 2 receptors are involved in Ucn1‐stimulated ion secretion, while Ucn2‐ and Unc3‐stimulated ion secretion is mediated by the CRF 2 receptors. Ucn2 and Ucn3 are more potent than CRF in stimulation of colonic ion secretion and may play a dominant role in stress‐induced hyper secretion and diarrhea. Support or Funding Information NIH R15 DK097460‐01A1 (SL) and UWL graduate research service and educational leadership grant (AK). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .