Background: CB-1 receptor agonists reduce cholinergic neurotransmission and intestinal propulsion.
The reduction of intestinal propulsion might partially be due to CB-1 effects on neuronal
circuits like the peristaltic reflex.
Aim: Aim of the study was to investigate the influence of the CB-1 receptor on gastrointestinal
motility by using the antagonist AM251 and the agonist Anadamide (AEA) in models of
the peristaltic reflex, the gastrointestinal transit and small intestinal electrophysiology.
Methods: Segments of isolated rat ileum were studied in a chambered organ bath. The reflex
was initiated by electrical stimulation and 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, only allowing the ileum to pass, separating the
buffer of stimulation and recording sites. The intestinal transit was evaluated in
vivo in CB-1 receptor knockout (KO) and wildtype mice. Additionally electrophysiological
properties of neuromuscular interaction were evaluated using standard intracellular
recording techniques in both genotypes.
Results: AM251 significantly stimulated the force of the ARPPR in concentration dependent
manner in wildtypes. This effect was not abolished in presence of AEA (AM251: 10-9M3,5±7,9%; 10-8M:11,8±9,5%; 10-7M:23,7±10,0%; 10-6M: 29,4±11,5%; 10-5M: 49,9±9,4%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%). Neither AM251 nor AEA had an influence on the timing regardless the
chamber it was applied. CB-1 deficient mice displayed an 40% accelerated transit compared
to control mice. Resting membrane potentials and neuronally induced inhibitory junction
potentials in CB-1 KO mice are unchanged compared to wildtype littermates.
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 KO mice gastrointestinal transit is significantly increased, suggesting
the CB-1 receptor as a promising target for the treatment of motility disorders.
