Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis

Eur J Pharmacol. 2017 Feb 5:796:7-19. doi: 10.1016/j.ejphar.2016.12.004. Epub 2016 Dec 7.

Abstract

The importance of cyclooxygenase and lipoxygenase pathways and the consequent eicosanoid synthesis in the physiology and pathophysiology of the intestinal epithelium is currently being established. Each eicosanoid (prostanoid, leukotriene, hydroxyeicosatetraenoic acid) preferentially recognizes one or more receptors coupled to one or more signal-transduction processes. This overview focuses on the role of eicosanoid receptors in the maintenance of intestinal epithelium physiology through the control of proliferation/differentiation/apoptosis processes. Furthermore, it is reported that the role of these receptors on the regulation of the barrier function of the intestinal epithelium have arisen through the regulation of absorption/secretion processes, tight-junction state and the control of the intestinal immune response. Also, this review considers the implication of AA cascade in the disruption of epithelial homeostasis during inflammatory bowel diseases and colorectal cancer as well as the therapeutic values and potential of the eicosanoid receptors as novel targets for the treatments of the pathologies above mentioned.

Keywords: 12-Hydroxyheptadecatrenoic acid (PubChem CID:5283141); Arachidonic acid cascade; Butaprost acid (PubChem CID: 25886893); Carbacyclin (PubChem CID:6436393); Colorectal cancer; G protein-coupled receptor; Gastrointestinal physiology; Inflammatory bowel diseases; Leukotriene B(4) (PubChem CID: 5280492); Leukotriene D(4) (PubChem CID: 5280878); Lipoxin A(4) (PubChem CID:5280914); Prostaglandin E(2) (PubChem CID: 5280360); Sulprostone (PubChem CID: 5312153); Tomelukast (PubChem CID: 3969); U75302 (PubChem CID:6449854).

Publication types

  • Review

MeSH terms

  • Animals
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Homeostasis* / drug effects
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Molecular Targeted Therapy / methods*
  • Receptors, Eicosanoid / metabolism*

Substances

  • Receptors, Eicosanoid