BACKGROUND AND PURPOSE
Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to
modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier
integrity. The aim of the present study was to determine whether cannabinoids modulate the increased permeability
associated with inflammation in vitro.
Confluent Caco-2 cell monolayers were treated for 24 h with IFNg and TNFa (10 ng·mL-1
). Monolayer permeability was
measured using transepithelial electrical resistance and flux measurements. Cannabinoids were applied either apically or
basolaterally after inflammation was established. Potential mechanisms of action were investigated using antagonists for CB1,
CB2, TRPV1, PPARg and PPARa. A role for the endocannabinoid system was established using inhibitors of the synthesis and
degradation of endocannabinoids.
-Tetrahydrocannabinol (THC) and cannabidiol accelerated the recovery from cytokine-induced increased permeability; an
effect sensitive to CB1 receptor antagonism. Anandamide and 2-arachidonylglycerol further increased permeability in the
presence of cytokines; this effect was also sensitive to CB1 antagonism. No role for the CB2 receptor was identified in these
studies. Co-application of THC, cannabidiol or a CB1 antagonist with the cytokines ameliorated their effect on permeability.
Inhibiting the breakdown of endocannabinoids worsened, whereas inhibiting the synthesis of endocannabinoids attenuated,
the increased permeability associated with inflammation.
CONCLUSIONS AND IMPLICATIONS
These findings suggest that locally produced endocannabinoids, acting via CB1 receptors play a role in mediating changes in
permeability with inflammation, and that phytocannabinoids have therapeutic potential for reversing the disordered intestinal
permeability associated with inflammation.