Targeting cholinergic system to modulate liver injury

Ravirajsinh N. Jadeja, Vikrant P. Rachakonda, Sandeep Khurana

Research output: Contribution to journalReview article

Abstract

Over the past few decades, evidence accumulated to indicate that parasympathetic innervation regulates liver injury and regeneration. Liver derives its parasympathetic input via vagus nerve. In animal models, vagus nerve stimulation and transection are frequently used to determine the impact of parasympathetic input on liver injury responses. Such strategies provide limited understanding of postneuronal mechanisms involved in the regulation of liver injury. The hepatic branch of vagus nerve releases acetylcholine (ACh), which activates muscarinic and nicotinic receptors in hepatocytes as well as non-parenchymal cells to modulate cellular functions. Moreover, vagus nerve releases other neurotransmitters such as vasoactive intestinal peptide (VIP), which also modulates liver injury responses and hemodynamics. Therefore, our understanding of the post-neuronal modulation of liver injury in models utilizing vagus nerve activity remains limited. Gene-silencing technologies and pharmacological manipulation of receptor activity have not only improved our understanding of the role of specific cholinergic receptors but also elucidated the role of various liver cell sub-populations in modulating liver injury response. With advent of organ- and cell-specific transgenic mice, our understanding of neural regulation of liver injury is likely to improve further. This review comprehensively provides current understanding of cholinergic regulation of liver injury, and points to potential therapeutic targets to treat liver injury.

Original languageEnglish (US)
Pages (from-to)938-944
Number of pages7
JournalCurrent drug targets
Volume19
Issue number8
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Liver
Cholinergic Agents
Wounds and Injuries
Vagus Nerve
Vagus Nerve Injuries
Vagus Nerve Stimulation
Liver Regeneration
Vasoactive Intestinal Peptide
Nicotinic Receptors
Hemodynamics
Gene Silencing
Cholinergic Receptors
Muscarinic Receptors
Transgenic Mice
Acetylcholine
Neurotransmitter Agents
Hepatocytes
Animals
Animal Models
Genes

Keywords

  • Liver injury
  • Muscarinic receptors
  • Nicotinic receptors
  • Parasympathetic nervous system

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Targeting cholinergic system to modulate liver injury. / Jadeja, Ravirajsinh N.; Rachakonda, Vikrant P.; Khurana, Sandeep.

In: Current drug targets, Vol. 19, No. 8, 01.01.2018, p. 938-944.

Research output: Contribution to journalReview article

Jadeja, Ravirajsinh N. ; Rachakonda, Vikrant P. ; Khurana, Sandeep. / Targeting cholinergic system to modulate liver injury. In: Current drug targets. 2018 ; Vol. 19, No. 8. pp. 938-944.
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