CB1 and TRPV1 receptors mediate protective effects on colonic electrophysiological properties in mice.
J Mol Med. 2006-02-25; 84(6): 513-520
DOI: 10.1007/s00109-006-0040-x
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1. J Mol Med (Berl). 2006 Jun;84(6):513-20. Epub 2006 Feb 25.
CB1 and TRPV1 receptors mediate protective effects on colonic
electrophysiological properties in mice.
Sibaev A(1), Massa F, Yüce B, Marsicano G, Lehr HA, Lutz B, Göke B, Allescher HD,
Storr M.
Author information:
(1)Department of Internal Medicine II and Institute of Surgical Research,
Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377, Munich, Germany.
CB1 and TRPV1 receptors modulate enteric neurotransmission and colonic
inflammation. This study investigates early electrophysiological changes in
distal colon of wild-type and receptor deficient mice after an inflammatory
insult set by dinitrobenzene sulfonic acid (DNBS). Colitis was induced by DNBS in
CB1(-/-) mice, TRPV1(-/-) mice, and their respective wild-type littermates.
Electrophysiological properties consisting of membrane potentials and
electrically induced inhibitory junction potentials (IJP) of circular smooth
muscle cells were evaluated at different time points. Additionally a histological
colitis severity score was evaluated in CB1(+/+) and CB1(-/-) mice 24 h after
DNBS. Inflammation caused spontaneous atropine insensitive rhythmic action
potentials in CB1(-/-) and TRPV1(-/-) mice but not in wild-type animals. This
indicates that membrane stability is disturbed, which in turn indicates a lack of
protective mechanisms. Focal electrical neuronal stimulation of the myenteric
plexus induced IJP in the smooth muscle cells. Twenty-four hours after initiation
of inflammation, the duration of the IJP is prolonged in all animals, indicating
disturbances within neuromuscular interaction. In CB1(-/-) mice, it is
interesting that the duration of IJP was significantly extended, as compared to
CB1(+/+) mice pointing toward missing protective mechanisms in the CB1(-/-) mice.
Inflammatory insults in the mouse colon induce reproducible changes in the
electrophysiological properties and such changes correlate with duration of
colitis. In mutants, these electrophysiological changes display different
patterns, suggesting the lack of protective properties for neuromuscular
interactions and membrane stability.
DOI: 10.1007/s00109-006-0040-x
PMID: 16501934 [Indexed for MEDLINE]