Corticotropin-releasing factor receptor 1 (CRF-R1) antagonists: Promising agents to prevent visceral hypersensitivity in irritable bowel syndrome

Peptides. 2022 Jan:147:170705. doi: 10.1016/j.peptides.2021.170705. Epub 2021 Nov 22.

Abstract

Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that coordinates the endocrine system, autonomic nervous system, immune system, and physiological behavior. CRF is a signaling regulator in the neuro-endocrine-immune (NEI) network that mediates visceral hypersensitivity. Rodent models to simulate changes in intestinal motility similar to those reported in the irritable bowel syndrome (IBS), demonstrate that the CRF receptor 1 (CRF-R1) mediates intestinal hypersensitivity under many conditions. However, the translation of preclinical studies into clinical trials has not been successful possibly due to the lack of sufficient understanding of the multiple variants of CRF-R1 and CRF-R1 antagonists. Investigating the sites of action of central and peripheral CRF is critical for accelerating the translation from preclinical to clinical studies.

Keywords: Corticotropin-releasing factor receptor 1; Irritable bowel syndrome; Visceral hypersensitivity.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Corticotropin-Releasing Hormone / metabolism*
  • Gastrointestinal Motility / physiology
  • Humans
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / etiology*
  • Irritable Bowel Syndrome / psychology
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Receptors, Corticotropin-Releasing Hormone / metabolism

Substances

  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone