CB2 cannabinoid receptor agonist selectively inhibits the mechanosensitivity of mucosal afferents in the guinea pig bladder.
Bladder afferents play a pivotal role in bladder function such as urine storage and micturition, and conscious sensations such as urgency and pain. Endocannabinoids are ligands of cannabinoid receptors 1 and 2 (CB1 and CB2) but can influence activity of a variety of G protein coupled receptors, and ligand and voltage gated channels. It is still not known which classes of bladder afferents are influenced by the CB1 and CB2 receptor agonists. This study aimed to determine the role of the CB2 receptors in two major classes of afferents in the guinea pig bladder, mucosal and muscular mucosal. The mechanosensitivity of these two classes was determined by an ex vivo extracellular electrophysiological recording technique. A stable analogue of endocannabinoid anandamide, methanandamide (mAEA) potentiated the mechanosensitivity of mucosal bladder afferents in response to stroking. In the presence of TRPV1 antagonist (capsazepine) the effect of mAEA switched from excitatory to inhibitory. The selective CB2 receptor agonist, 4 quinolone 3 carboxyamide (4Q3C) significantly inhibited the mechanosensitivity of mucosal bladder afferents to stroking. In the presence of a CB2 receptor antagonist, the inhibitory effect of 4C3F was lost. mAEA and 4Q3C did not affect responses to stretch and/or mucosal stroking of muscular mucosal afferents. Our findings revealed that agonists of the CB2 receptors selectively inhibited the mechanosensitivity of capsaicin sensitive mucosal bladder afferents, but not muscular mucosal afferents. This may have important implications for understanding of the role of endocannabinoids in modulating bladder function and sensation in health and diseases.
American journal of physiology. Renal physiology