Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract

Abstract

The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover. Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes. A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain. The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract. CB1 receptor immunoreactivity was observed in the lamina propria and epithelial cells. CB2 receptor immunoreactivity was expressed by lamina propria mast cells and immunocytes, blood vessels, and smooth muscle cells. Faint CB2 receptor immunoreactivity was also observed in neurons and glial cells of the submucosal plexus. GPR55 receptor immunoreactivity was expressed by lamina propria macrophages and smooth muscle cells. PPARα receptor immunoreactivity was expressed by blood vessels, smooth muscle cells, and glial cells of the myenteric plexus. Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog. Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.

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Acknowledgements

We are thankful to Dr. Giovanni Marsicano (INSERM U1215, NeuroCentre Magendie, Team ‘Endocannabinoids and Neuroadaptation’, Bordeaux, France) and to Prof. Giovanna Zoccoli (Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna) who kindly provided us with brain sample of wild-type and mice with congenital deficiency of CB1. We are thankful to Dr. Catia Barboni (Department of Veterinary Medical Sciences, Alma Mater Studiorum—University of Bologna), who kindly provided us with samples of mouse intestine for the Wb analysis, and with Dr. Marco Luppi (Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum—University of Bologna) who kindly provided with sample of rat intestine for wholemount preparations.

Funding

This research received a grant from Innovet Italia S.r.l. (2017).

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Correspondence to Roberto Chiocchetti.

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Galiazzo, G., Giancola, F., Stanzani, A. et al. Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract. Histochem Cell Biol 150, 187–205 (2018). https://doi.org/10.1007/s00418-018-1684-7

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Keywords

  • Enteric nervous system
  • Immunohistochemistry
  • Inflammatory bowel disease
  • Mast cells
  • Palmitoylethanolamide