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Peristalsis is impaired in the small intestine of mice lacking the P2X 3 subunit
Author(s) -
Bian Xiaochun,
Ren Jianhua,
Vries Matthew,
Schnegelsberg Birthe,
Cockayne Debra A.,
Ford Anthony P. D. W.,
Galligan James J.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00309.x
Subject(s) - peristalsis , protein subunit , small intestine , anatomy , medicine , biology , endocrinology , genetics , gene
P2X receptors are ATP‐gated cation channels composed of one or more of seven different subunits. P2X receptors participate in intestinal neurotransmission but the subunit composition of enteric P2X receptors is unknown. In this study, we used tissues from P2X 3 wild‐type (P2X 3 +/+ ) mice and mice in which the P2X 3 subunit gene had been deleted (P2X 3 −/− ) to investigate the role of this subunit in neurotransmission in the intestine. RT‐PCR analysis of mRNA from intestinal tissues verified P2X 3 gene deletion. Intracellular electrophysiological methods were used to record synaptic and drug‐induced responses from myenteric neurons in vitro . Drug‐induced longitudinal muscle contractions were studied in vitro . Intraluminal pressure‐induced reflex contractions (peristalsis) of ileal segments were studied in vitro using a modified Trendelenburg preparation. Gastrointestinal transit was measured as the progression in 30 min of a liquid radioactive marker administered by gavage to fasted mice. Fast excitatory postsynaptic potentials recorded from S neurons (motoneurons and interneurons) were similar in tissues from P2X 3 +/+ and P2X 3 −/− mice. S neurons from P2X 3 +/+ and P2X 3 −/− mice were depolarized by application of ATP but not α,β‐methylene ATP, an agonist of P2X 3 subunit‐containing receptors. ATP and α,β‐methylene ATP induced depolarization of AH (sensory) neurons from P2X 3 +/+ mice. ATP, but not α,β‐methylene ATP, caused depolarization of AH neurons from P2X 3 −/− mice. Peristalsis was inhibited in ileal segments from P2X 3 −/− mice but longitudinal muscle contractions caused by nicotine and bethanechol were similar in segments from P2X 3 +/+ and P2X 3 −/− mice. Gastrointestinal transit was similar in P2X 3 +/+ and P2X 3 −/− mice. It is concluded that P2X 3 subunit‐containing receptors participate in neural pathways underlying peristalsis in the mouse intestine in vitro . P2X 3 subunits are localized to AH (sensory) but not S neurons. P2X 3 receptors may contribute to detection of distention or intraluminal pressure increases and initiation of reflex contractions.