Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon

Pharmacological characterization of cannabinoid receptor activity in the rat‐isolated ileum myenteric plexus‐longitudinal muscle preparation

“…The inability of SR 144528 to antagonize the inhibitory effects of each of the four agonists, and of capsazepine to block the effect of AEA under both EFS conditions, suggested that neither the CB2 nor TRPV1 receptor mediated the inhibition of both types of the EFS-evoked contractions. This result was consistent with previous data from similar in vitro contraction studies on the guinea pig and human ileal MPLM Mang et al 2001;Manara et al, 1998), and in vivo studies evaluating the inhibitory effect of these cannabinoids on small intestinal transit in both the rat and mouse (Izzo et al, 1999;.…”

“…The former action has been invariably studied by evaluating either the distance travelled or the delay in the time taken for the transit of an orally or intra-duodenally administered non-absorbable marker from the pylorus to the caecum of the animal. While in vivo bioassays have played an important role in characterizing the pharmacology of cannabinoids on intestinal motility under both physiological and pathophysiological states, the mechanism of the depressant action has been inferred from in vitro studies performed on segments or strips of the isolated ileum of the guinea pig Coutts and Pertwee, 1997;Izzo et al, 1998;Mang et al, 2001), and, to a lesser extent, of a human Manara et al, 1998;Guagnini et al, 2006). Therefore, to date, the guinea pig ileum has been the standard in vitro bioassay for screening cannabinoids on the small intestine.…”

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…A functional role for endocannabinoids and CB 1 receptors in the gastrointestinal tract is supported by pharmacological studies demonstrating that anandamide and various CB 1 agonists (WIN 55,212-2, CP55,940, and ACEA) but not the CB 2 -selective agonists JWH-133 inhibit gastrointestinal motility in rodents in vivo and in isolated ileum and colon from both experimental animals and humans (Shook and Burks, 1989;Pertwee et al, 1995Pertwee et al, , 1996Coutts and Pertwee, 1997;McCallum et al, 1999;Mancinelli et al, 2001;Mang et al, 2001;Landi et al, 2002;Manara et al, 2002;Hinds et al, 2006). A similar role for endogenous substrates of FAAH is suggested by recent in vivo findings in mice, documenting inhibition of intestinal motility by the FAAH inhibitors N-arachidonoylserotonin and palmitoylisopropylamide and by the FAAH substrates palmitoylethanolamide, oleamide, and oleoylethanolamide in wildtype but not in FAAH knockout mice (Capasso et al, 2005).…”

Drugs Affecting Visceral Sensitivity: Ready for the Prime Time?

“…Activation of the CB-1 receptor by agonists results in inhibition of intestinal motility through a reduction cholinergic excitatory inputs [31] , and on the other hand, cannabinoid receptor agonists might reduce hyperalgesia [32] , secondary to their effects on visceral afferent pathways. Despite these indirect arguments, no study has been undertaken to evaluate the effect of CB ligands on visceral sensitivity.…”