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

Roberto Chiocchetti,Ester Grilli,Giorgia Galiazzo,Andrea Toschi,Gemma Mazzuoli-Weber,Claudio Tagliavia,Andrea Piva

doi:10.3390/ani11020263

Abstract

Simple SummaryThe 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.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.

Highlights

The network of sensory neurons, motor neurons, interneurons, and glial cells embedded in the gut walls is called the enteric nervous system (ENS) [1]
In the gastrointestinal tract (GIT), cannabinoid receptors regulate motility, secretion, emesis, food intake, and inflammation [15,17,24,26]. The authors focused their attention on the presence of the endocannabinoid system (ECS) in the ileal myenteric plexus (MP) of pigs, with particular emphasis on both the cannabinoid receptors, namely CB1R and CB2R, and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and 5-HT1a serotonin receptor (5-HT1aR) by carrying out immunohistochemical analysis
The large percentages of CB1R and TRPV1immunoreactive neurons, which we found in the porcine MP ileum, allowed us to speculate that CB1R and TRPV1 may co-exist on the same subclass of cholinergic neurons as substantiated by functional and immunohistochemical studies [35,63]

Summary

Introduction

The network of sensory neurons, motor neurons, interneurons, and glial cells embedded in the gut walls is called the enteric nervous system (ENS) [1]. There is a strict interaction between the ENS and the central nervous system (CNS), with a bidirectional information flow between these two systems; the ENS can control digestive functions independently of the CNS [3]. The ENS cooperates with the immune and endocrine systems by adapting nutrient absorption depending on the condition of the gut, thereby preserving mucosal barrier functionality [3]. The endocannabinoid system (ECS) is constituted of three fundamental components: receptors, signaling molecules, and the enzymes responsible for ligand biosynthesis and degradation. It typically comprises the prototypical cannabinoid receptors types 1 and

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