Cannabinoid receptor 2 is increased in acutely and chronically inflamed bladder of rats

Abstract

Cannabinoid receptors 1 and 2 (CB1 and CB2) are G-protein coupled receptors that are expressed throughout the body. Cannabinoid receptor are expressed in the urinary bladder and may affect bladder function. The purpose of this study was twofold: to confirm the presence of cannabinoid receptors in the bladder, the L6/ S1 spinal cord, and dorsal root ganglia (DRG), and to determine the effects of acute and chronic bladder inflammation on expression of cannabinoid receptors. Acute or chronic bladder inflammation was induced in rats by intravesical administration of acrolein. Abundance of CB1 and CB2 protein and their respective mRNA was determined using immunoblotting and quantitative real-time PCR, respectively. We confirmed the presence of CB1 and CB2 receptor protein and mRNA in bladder, L6-S spinal cord, and DRG. Acute bladder inflammation induced increased expression of CB2, but not CB1, protein in the bladder detrusor. Chronic bladder inflammation increased expression of bladder CB2 protein and mRNA but not CB1 protein or mRNA. Expression of CB1 or CB2 in spinal cord or DRG was unaffected by acute or chronic bladder inflammation. CB1 and CB2 receptors are present in the bladder and its associated innervation, and CB2 receptors are up-regulated in bladder after acute or chronic inflammation. CB2 receptors may be a viable target for pharmacological treatment of bladder inflammation and associated pain.Cannabinoid receptors 1 and 2 (CB1 and CB2) are members of the G-protein coupled receptor (GPCR) superfamily. CB1 is expressed primarily in the central nervous system (CNS) and is the most abundant GPCR in the brain [19]. CB2 is expressed by leukocytes, including mast cells [6], lymphocytes, monocytes, and neutrophils [2], and CB2 is also expressed at low levels in the CNS in both microglia and some neurons [8,22]. Cannabinoid receptors have also been detected in peripheral tissues, including urinary bladder [10]. Endocannabinoids and cannabinoid agonists decrease motility in normal and inflamed bladder, suggesting that CB receptors may have functional effects on the bladder [4,12,13]. Hyperalgesia associated with turpentine-induced acute bladder inflammation was prevented by administration of a cannabinoid agonist [6]. While there is interest in the use of cannabinoids to treat bladder disorders, effects of inflammation on expression of cannabinoid receptors in the bladder have not been described.*Address correspondence to: Dr. Dale E. Bjorling, Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive Drive, Madison, WI 53706, bjorlind@svm.vetmed.wisc.edu, Tel: 608-263-4808, Fax: 608-263-7930. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the productio...

Cannabinoid receptor expression in the bladder is altered in detrusor overactivity

“…It will be interesting for future studies to clarify this by using co-localisation of nerve fibres with CB1 receptors to identify the type of nerve fibres altered in the suburothelium and detrusor of patients with DO. A role for CB2 receptors in bladder dysfunction has been suggested by the finding of upregulation of receptor expression in rat bladders with acute and chronic inflammation [24] and in MS patients with neurogenic DO [23]. Similarly, we found increased CB2 receptor expression in the mucosa of patients with DO and a decrease in receptor expression in the detrusor of these patients, suggesting altered CB2 function in the urinary bladder that is related to disease.…”

Is There Any Clinically Relevant Cannabinoid-Induced Analgesia?

“…Since then, it has been shown that a number of different CB 2 R agonists can modulate many types of pain, i.e. acute, inflammatory, neuropathic, post-surgical and cancer pain [33,34,35,36,37,38,39,40,41,42,43,44]. It is still not completely clear where these CB 2 R agonists exert their analgesic activity.…”

“…In several experiments, spinal cannabinoid CB 2 Rs were not up-regulated by different inflammatory processes such as CFA-induced paw inflammation [42] and CFA-induced arthritis [43] or acrolein-induced bladder inflammation in rats [44]. …”

Cannabinoids and the Urinary Bladder

“…Similarly, the presence of the endocannabinoid system in the urinary bladder has led to speculation that endocannabinoid-signalling is involved in the signal transduction pathways regulating bladder relaxation and may be involved in pathophysiological processes of the bladder. This role of the endocannabinoids in the lower urinary tract supports their therapeutic potential in conditions of OAB and DO, whereas evidence already exists for their role in bladder inflammation [2,59,75,84]. There are still a number of unanswered questions in the understanding of cannabinoid pharmacology in the urinary bladder.…”

“…CB 1 receptors are mainly found at the central and peripheral neuron terminals of the bladder, inhibiting neurotransmitter release [55]. Several studies have localized both cannabinoid receptors in the urinary bladder of humans rats mice and monkeys [2,[55][56][57][58][59][60]. The localization of CB 1 receptors has been described to be in the urothelium and nerve fibres of the suburothelium and in human and rat detrusor muscle [2,58,60].…”