Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

Neurogastroenterol Motil. 2011 Mar;23(3):265-70, e120-1. doi: 10.1111/j.1365-2982.2010.01661.x.

Abstract

Background: Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility.

Methods: Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro-Gold (FG) and fluo-immunohistochemistry staining.

Key results: 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD-E), and 44.4% showed inhibition (GD-I). After GD, the firing rate of GD-E neurons significantly increased (P<0.01), but decreased for GD-I neurons (P<0.01). Most of both GD-E and GD-I neurons were activated by motilin (P<0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P<0.05-0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P<0.05). Motilin/FG-labeled neurons were detected in hypothalamus paraventricular nucleus (PVN).

Conclusions & inferences: Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology*
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / physiology
  • Gastrointestinal Agents / pharmacology*
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology*
  • Male
  • Motilin / pharmacology*
  • Neurons / drug effects*
  • Neurons / physiology
  • Paraventricular Hypothalamic Nucleus / cytology
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • GM 109
  • Gastrointestinal Agents
  • Peptides, Cyclic
  • Motilin