Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype

Burdyga G, Varro A, Dimaline R, Thompson DG, Dockray GJ. Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype. Am J Physiol Gastrointest Liver Physiol 299: G63-G69, 2010. First published April 29, 2010; doi:10.1152/ajpgi.00059.2010.-The intestinal hormone cholecystokinin (CCK) inhibits food intake via stimulation of vagal afferent neurons (VAN). Recent studies suggest that CCK also regulates the expression of some G protein-coupled receptors and neuropeptide transmitters in these neurons. The aim of the present study was to characterize the expression of cannabinoid (CB) 1 receptors in VAN and to determine whether stimulation of these receptors plays a role in regulating neurochemical phenotype. Expression of CB1 in rat VAN was detectable by in situ hybridization or immunohistochemistry after 6 h of fasting and increased to a maximum after 24 h when similar to 50% of neurons in the mid and caudal regions expressed the receptor. Melanin-concentrating hormone (MCH)1 receptors also increased with fasting, but the changes were delayed compared with CB1; in contrast Y2 receptors (Y2R) exhibited reciprocal changes in expression to CB1. Administration of CCK8s (10 nmol ip) to fasted rats decreased expression of CB1 with a t(1/2) of similar to 1 h compared with 3 h for MCH1. The action of CCK8s was inhibited by ghrelin and orexin-A. The CB1 agonist anandamide (intraperitoneally) reversed the effect of CCK8s on CB1, MCH1, and Y2 receptor expression. In contrast, in rats fasted for 18 h, administration of a CB1 antagonist/inverse agonist (AM281 ip) downregulated CB1 expression and increased Y2 receptor expression. Activation of vagal CB1 receptors therefore influences the neurochemical phenotype of these neurons, indicating a new and hitherto unrecognized role for endocannabinoids in gut-brain signaling.