Evaluation of the effect of age on cannabinoid receptor functionality and expression in guinea-pig ileum longitudinal muscle-myenteric plexus preparations

Cannabinoid drugs exert a wide range of biological effects and are currently under study for their multiple potential therapeutic uses. Cannabinoids reduce gastrointestinal (GI) motility and this is mediated by the CB1 cannabinoid receptor (CB1R) present in the myenteric neurones. GI motility can also be affected by a variety of pathophysiological situations, including ageing. The purpose of this work was to study the influence of age on the functionality and expression of CB1R in the myenteric plexus. Ileal longitudinal muscle-myenteric plexus (LMMP) preparations from young, adult and old guinea-pigs were used in two sets of experiments: in vitro assessment of the inhibitory cannabinoid effect upon electrically stimulated contractions and immunohistochemical quantification of myenteric neurones expressing CB1R. LMMP preparations responded to the synthetic cannabinoid WIN 55,212-2, and the endogenous cannabinoid ligand anandamide in an age-independent manner. The total number of CB1R-immunoreactive (IR) myenteric neurones, which included at least part of the motor neurones to the longitudinal smooth muscle, decreased in proportion to the general neuronal population; however, the proportion of CB1R-IR neurones was preserved in old animals. These data may justify the preservation of the effectiveness of the cannabinoids in the isolated guinea-pig ileum. This age-related independency of CB1R expression and effect on GI motility could be of interest if cannabinoids are to be used therapeutically.