Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of intestinal motor responses within the myenteric part of the peristaltic reflex.
Neurogastroenterol Motil. 2007-09-01; 19(9): 744-753
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1. Neurogastroenterol Motil. 2007 Sep;19(9):744-53.
Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of
intestinal motor responses within the myenteric part of the peristaltic reflex.
Yuece B(1), Sibaev A, Broedl UC, Marsicano G, Göke B, Lutz B, Allescher HD, Storr
(1)Department of Internal Medicine II and Institute of Surgical Research,
Ludwig-Maximilians University Munich, Munich, Germany.
Cannabinoid-1 (CB1) receptor activation affects gastrointestinal propulsion in
vivo. It was our aim to further characterize the involved myenteric mechanisms in
vivo and in vitro. In CB1(-/-) mice and wild-type littermates we performed in
vivo transit experiments by charcoal feeding and in vitro electrophysiological
recordings in mouse small intestinal smooth muscle. Ascending neuronal
contraction (ANC) following electrical field stimulation was studied in rat ileum
in a partitioned organ bath separating the aboral stimulation site from the oral
recording site. The knockout animals displayed an accelerated upper
gastrointestinal transit compared to control animals. The CB1 receptor antagonist
AM251 stimulated the force of the ANC in a concentration dependent manner when
added in the oral chamber. Anandamide significantly inhibited the ANC when added
in the oral chamber. Neither AM251 nor anandamide had an influence on the
contraction latency. No effects were observed when drugs were added in the aboral
chamber, proving a CB1 mediated action on the neuromuscular junction. Resting
membrane potentials and neuronal induced inhibitory junction potentials in
CB1(-/-) mice were unchanged as compared to wild type. However, the
electrophysiological slow waves were more sensitive to blockade of Ca(2+)
channels in CB1(-/-) mice. Our data strongly suggest a physiological involvement
of the CB-1 receptor in the regulation of small intestinal motility. Therefore,
CB1 receptors are a promising target for the treatment of motility disorders.
PMID: 17727394 [Indexed for MEDLINE]