Effects of Cannabinor, a Novel Selective Cannabinoid 2 Receptor Agonist, on Bladder Function in Normal Rats

Background: Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established. Objectives: Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function. Design, setting, and participants: Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated. Measurements: Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used. Results and limitations: CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0 mg/kg increased micturition intervals and volumes by 52% (p < 0.05) and 96% (p < 0.01), respectively, and increased threshold and flow pressures by 73% (p < 0.01) and 49% (p < 0.001), respectively. Cannabinor 0.3 or 1.0 mg/kg or vehicle did not affect urodynamic parameters. Conclusions: Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on afferent'' urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited. (c) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.