Cannabinoid-1 Rezeptoren (CB1) beeinflussen die Motilität des Dünndarms von Maus und Ratte

Background: CB-1 receptors are involved in neurotransmission of the
GI-tract and thus motility phenomena. The effect of intestinal
propulsion might partially be due to CB-1 receptor mediated effects
on neuronal circuits like the peristaltic reflex. Aim: Aim of the
study was to further characterize the influence of CB-1 receptors
on small intestinal motility by using antagonists and the agonists
in established in vivo and in vitro models. Methods: Segments of
isolated rat ileum were studied in a chambered organ bath. The
reflex was initiated by electrical stimulation, force and timing of
the ascending reflex pathways of the myenteric part of the
peristaltic reflex (ARPPR) of ileum were recorded. Chambers were
separated by a baffle, allowing the ileum to pass, separating the
stimulation and recording sites. The intestinal transit was
evaluated in vivo in CB-1 receptor knockout (CB-1 -/-) and wildtype
mice. Additionally electrophysiological properties of neuromuscular
interaction were evaluated using standard intracellular recording
techniques in both genotypes. Results: CB-1 deficient mice
displayed an 40% accelerated transit compared to control mice. When
applied into the recording chamber AEA significantly inhibited the
ARPPR in a concentration dependent manner (10-9M 2,3±3,7%;
10-8M:-1,0±4,6%; 10-7M: 3,8±7,1%; 10-6M:13,1±5,8%; 10-5M:32,7±7,8%)
in a CB-1 sensitive manner. Neither AM251 nor AEA had an influence
on the timing regardless the chamber it was applied. AM251
significantly stimulated the force of the ARPPR in concentration
dependent manner (AM251: 10-8M:11,8±9,5%; 10-7M:23,7±10,0%; 10-6M:
29,4±11,5%; 10-5M: 49,9±9,4%) Resting membrane potentials and
neuronally induced inhibitory junction potentials in CB-1 KO mice
are unchanged compared to wildtype littermates, however, the
electrophysiological slow waves are more sensitive to blockade of
Ca2+ channels in CB-1 -/- mice. Conclusions: The results indicate
that antagonism at the CB-1 receptors exhibited a strong
enhancement of the ARPPR whereas agonism at the CB-1 receptor
reduces the ARPPR. The concept holds true since in CB-1 -/- mice
small intestinal transit is significantly increased, suggesting the
CB-1 receptor as a promising target for the treatment of motility
disorders.