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Simple Summary  The endocannabinoid system (ECS) has opened the door to novel therapeutical approaches targeting cancer, pain, anxiety, stress, and inflammatory diseases. The ECS is ubiquitously expressed in almost all members of  Animalia , but its precise localization outside the central nervous system is still under investigation. In this study, the localization of the main and related cannabinoid receptors in the myenteric plexus of the porcine ileum was immunohistochemically analyzed. The myenteric plexus neurons were found to be positive for cannabinoid receptor 1 (CB1R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR). In addition, the ECS receptors were also located on nerve fibers, the  tunica muscularis , and the endothelium. The wide distribution of cannabinoid and cannabinoid-related receptors in the myenteric plexus provides the anatomical basis for additional investigation, suggesting the possible role of the ECS in treating pathological conditions in livestock.    Abstract  An important piece of evidence has shown that molecules acting on cannabinoid receptors influence gastrointestinal motility and induce beneficial effects on gastrointestinal inflammation and visceral pain. The aim of this investigation was to immunohistochemically localize the distribution of canonical cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR) in the myenteric plexus (MP) of pig ileum. CB1R, TRPV1, TRPA1, and 5-HT1aR were expressed, with different intensities in the cytoplasm of MP neurons. For each receptor, the proportions of the immunoreactive neurons were evaluated using the anti-HuC/HuD antibody. These receptors were also localized on nerve fibers (CB1R, TRPA1), smooth muscle cells of  tunica muscularis  (CB1R, 5-HT1aR), and endothelial cells of blood vessels (TRPV1, TRPA1, 5-HT1aR). The nerve varicosities were also found to be immunoreactive for both TRPV1 and 5-HT1aR. No immunoreactivity was documented for CB2R. Cannabinoid and cannabinoid-related receptors herein investigated showed a wide distribution in the enteric neurons and nerve fibers of the pig MP. These results could provide an anatomical basis for additional research, supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders in porcine enteropathies.

Cannabinoid and Cannabinoid-Related Receptors in the Myenteric Plexus of the Porcine Ileum