Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats

Gastroenterology. 2000 Dec;119(6):1569-79. doi: 10.1053/gast.2000.20251.


Background & aims: Corticotropin-releasing factor (CRF) exerts its action through CRF receptors 1 and 2 (CRF-R1 and CRF-R2). CRF has preferential affinity for CRF-R1, whereas urocortin displays high affinity for both. We investigated changes in colonic motor function after intraperitoneal (IP) injection of CRF-related peptides.

Methods: Colonic motility was recorded in vivo in conscious rats equipped with electrodes chronically implanted in the cecum and proximal colon or in vitro in distal colon; fecal output was monitored in naive rats.

Results: Rat CRF, rat urocortin, and amphibian sauvagine (10 microg/kg, IP) induced a new pattern of cecocolonic myoelectric activity characterized by clustered spike bursts of long duration; the percentage of occurrence was highest after CRF. The rank order of potency to increase fecal pellet output after IP peptide injection (0.3-10 microg/kg, IP) was CRF > urocortin = sauvagine. The CRF-R1/R2 antagonist astressin (33 microg/kg, IP) and the CRF-R1 antagonist CP-154,526 (20 mg/kg, subcutaneously) inhibited IP CRF-induced changes in cecocolonic myoelectric activity and IP CRF- and water avoidance stress-induced fecal output. In vitro, CRF injected into the inferior mesenteric artery increased distal colonic myoelectric activity compared with saline injection.

Conclusions: These results demonstrate that CRF acts peripherally to stimulate colonic motility and that CRF-R1 is primarily involved in mediating IP CRF/urocortin- and water avoidance stress-induced colonic motor response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avoidance Learning
  • Colon / drug effects
  • Colon / physiopathology*
  • Corticotropin-Releasing Hormone / pharmacology
  • Corticotropin-Releasing Hormone / physiology*
  • Defecation / drug effects
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Male
  • Myoelectric Complex, Migrating / drug effects
  • Peptide Fragments / pharmacology
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / physiology*
  • Stress, Physiological / chemically induced
  • Stress, Physiological / etiology
  • Stress, Physiological / physiopathology*
  • Urocortins
  • Water


  • CP 154526
  • Peptide Fragments
  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • Urocortins
  • Water
  • astressin
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone