Localisation of cannabinoid CB₁ receptor immunoreactivity in the guinea pig and rat myenteric plexus

Abstract

Activation of cannabinoid CB(1) receptors inhibits gastrointestinal motility, propulsion, and transit, whereas selective antagonism of these receptors has the opposite effects, suggesting the presence of endocannabinoid tone. Supporting evidence for presynaptic CB(1) receptors on myenteric neurons has been found in vitro. In this study, selective CB(1) receptor antibodies and neuronal markers were used to identify and characterise myenteric neurons expressing cannabinoid receptors. Whole mounts of rat and guinea pig myenteric preparations were dually labelled with antibodies against the CB(1) receptor and choline acetyltransferase, neurofilament proteins, calbindin, calretinin, synapsin I, microtubule-associated protein-2, calcitonin gene-related peptide, or substance P. The pattern of CB(1) receptor labelling and the neurochemical classification of CB(1) receptor-positive cells were markedly influenced by the species and fixation procedure. Virtually all choline acetyltransferase-immunoreactive myenteric neurons expressed CB(1) receptors in ganglia from both species. Subpopulations of neurons identified with calbindin, calretinin, and microtubule-associated protein-2 did not express CB(1) receptors. A few calcitonin gene-related peptide- and substance P-positive somata coexpressed CB(1) receptor immunoreactivity but showed little colocalisation on individual fibres. There was a close association between CB(1) receptor immunoreactivity and fibres labelled for synaptic protein, suggesting a role in the modulation of transmitter release. Functional responses to cannabinoids in the presence of hexamethonium suggest further that CB(1) receptors occur on excitatory motoneurons. In conclusion, CB(1) receptors are expressed on a variety of cholinergic sensory, interneuronal, and motor neurons in myenteric ganglia.

Pharmacological characterization of cannabinoid receptor activity in the rat‐isolated ileum myenteric plexus‐longitudinal muscle preparation

“…These data suggested all four agonists were full agonists at the CB1 receptor, and that their interaction with rimonabant could be simple competition. These results supported previous immunohistochemical and in vivo data describing the presence of the CB1 receptor in this tissue and its functional role in delaying small intestinal transit in vivo respectively (Izzo et al, 1999;Coutts et al, 2002).…”

Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves

“…This requires further electrophysiological investigations. CB 1 receptors have been described previously in the porcine and murine submucosal plexus (20,23) as they have in the myenteric plexus (9). In the pig, CB 1 receptor immunoreactivity was found colocalized with cholineacetyltransferase and substance P (23), which is consistent with observations we have made.…”

CB1Receptors Mediate the Analgesic Effects of Cannabinoids on Colorectal Distension-Induced Visceral Pain in Rodents

“…All three cannabinoid receptors are activated by endogenous lipid ligands known as endocannabinoids, with anandamide and 2-arachinodonyl glycerol being the most abundant endocannabinoids (for review, see Bisogno, 2008;. CB 1 receptors (CB 1 Rs) are mostly expressed in the nervous system at both central and peripheral sites, including the enteric nervous system (Matsuda et al, 1990(Matsuda et al, , 1992Ahluwalia et al, 2000;Coutts et al, 2002;Bridges et al, 2003;MacNaughton et al, 2004). In addition, CB 1 R expression has also been localized on normal colonic epithelium and smooth muscle (Casu et al, 2003;Ligresti et al, 2003).…”