Cannabinoids and the Urinary Bladder

Abstract

The presence of the Endocannabinoid System (ECS) 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. On the basis of this evidence, it was postulated that the binding of endocannabinoids to the cannabinoid receptors (CB 1 and CB 2 ) may result in relaxation of the urinary bladder during the filling phase. Dysregulation of the ECS in human bladder may be responsible for the aetiopathogenesis of Overactive Bladder Syndrome (OAB) and Detrusor Overactivity (DO).

A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors

“…The latter ones were also identified in detrusor cholinergic neurons and sensory suburothelial nerves expressing TRPV 1 and the calcitonin gene-associated peptide (CGRP) [45,55]. Furthermore, functional studies conducted by Bakali et al (2013) [48] showed that CB 2 receptors exerted both pre-and post-synaptic inhibitory effects on the contraction of the rat bladder, while CB 2 receptors exclusively act post-synaptically [49]. Stimulating both CB 1 andCB 2 receptors inhibits adenylyl cyclase from generating the cyclic-adenosine monophosphate (cAMP) by interaction with the α-subunit of the G protein of the G i/o family [56].…”

“…Furthermore, functional studies conducted by Bakali et al (2013) [48] showed that CB 2 receptors exerted both pre-and post-synaptic inhibitory effects on the contraction of the rat bladder, while CB 2 receptors exclusively act post-synaptically [49]. Stimulating both CB 1 andCB 2 receptors inhibits adenylyl cyclase from generating the cyclic-adenosine monophosphate (cAMP) by interaction with the α-subunit of the G protein of the G i/o family [56]. In turn, the orphan metabotropic GPR55 receptors (sometimes called CB 3 receptors) [57], among others, are also localized in the bladder [58], mainly in the urothelium [59].…”