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Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit

Xiaochun Bian1, Jianhua Ren, Matthew DeVries

  • 1Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.

The Journal of Physiology
|June 19, 2003
PubMed

Insights

The P2X3 subunit is crucial for intestinal peristalsis in mice, as its absence impairs reflex contractions. These P2X3 receptors are found on sensory neurons, likely detecting pressure changes to initiate gut motility.

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Molecular Biology

Background:

  • P2X receptors, ATP-gated cation channels, are involved in intestinal neurotransmission.
  • The specific subunit composition of enteric P2X receptors remains largely unknown.
  • Understanding P2X receptor roles is key to deciphering gut function and dysfunction.

Purpose of the Study:

  • To investigate the role of the P2X3 subunit in intestinal neurotransmission using P2X3 knockout mice.
  • To determine the localization of P2X3 subunits within the enteric nervous system.
  • To assess the impact of P2X3 subunit deletion on gastrointestinal motility and reflexes.

Main Methods:

  • Utilized P2X3 wild-type (P2X3+/+) and P2X3 knockout (P2X3-/-) mouse models.
  • Employed RT-PCR to confirm P2X3 gene deletion.
  • Performed intracellular electrophysiology on myenteric neurons, in vitro muscle contraction assays, and in vivo gastrointestinal transit measurements.

Main Results:

  • Fast excitatory postsynaptic potentials in S neurons were unaffected by P2X3 deletion.
  • P2X3 deletion abolished ATP-induced depolarization in AH (sensory) neurons, while S neurons remained responsive to ATP.
  • Peristalsis was significantly inhibited in P2X3-/- mice, though other muscle contractions and transit were normal.

Conclusions:

  • P2X3 subunit-containing receptors are essential components of the neural pathways regulating peristalsis in the mouse intestine.
  • P2X3 subunits are specifically localized to AH (sensory) neurons, not S neurons, in the enteric nervous system.
  • P2X3 receptors likely play a role in sensing intraluminal distention and initiating reflex contractions for gut motility.

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