Peripheral corticotropin-releasing factor (CRF) induces stimulation of gastric contractions in freely moving conscious rats: role of CRF receptor types 1 and 2

Neurogastroenterol Motil. 2013 Feb;25(2):190-7. doi: 10.1111/nmo.12050. Epub 2012 Dec 4.

Abstract

Background: Peripheral corticotrophin-releasing factor (CRF) plays an important role in stress-induced alterations of gastrointestinal motility. CRF injected peripherally inhibits gastric emptying, but its effect on gastric contractions has not been clarified in freely moving conscious rats.

Methods: Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after drug administration.

Key results: Subcutaneous injection (sc) of CRF (15 μg kg(-1)) increased the MI significantly. Pretreatment with intravenous astressin (100 μg kg(-1)), a non-selective CRF antagonist, blocked the sc CRF (15 μg kg(-1))-induced response, but astressin(2)-B (200 μg kg(-1), sc), a selective CRF receptor type 2 (CRF(2)) antagonist, enhanced the CRF-induced increase in MI significantly. Meanwhile urocortin 2 (15 μg kg(-1), sc), a selective CRF(2) agonist, did not alter the basal MI, but it inhibited the sc CRF (15 μg kg(-1))-induced stimulation of gastric contractions. The intraperitoneal injection of cortagine (30 μg kg(-1)), a selective CRF receptor type 1 (CRF(1)) agonist, mimicked the response induced by sc CRF.

Conclusions & inferences: Peripheral CRF stimulates gastric contractions through CRF(1). CRF(2) activation inhibits the response induced by CRF, suggesting that CRF(2) may have a modulatory action to CRF(1) signaling in gastric motor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRF Receptor, Type 1
  • Consciousness
  • Corticotropin-Releasing Hormone / metabolism*
  • Corticotropin-Releasing Hormone / pharmacology
  • Gastrointestinal Motility / physiology*
  • Male
  • Manometry / methods
  • Movement
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Stomach / drug effects
  • Stomach / physiology

Substances

  • CRF receptor type 2
  • Receptors, Corticotropin-Releasing Hormone
  • CRF Receptor, Type 1
  • Corticotropin-Releasing Hormone