Effects of nicotinic receptor agonists on bladder afferent nerve activity in an in vitro bladder-pelvic nerve preparation

Abstract

Effects of nicotinic receptor agonists (epibatidine and nicotine) on mechano-sensitive bladder afferent nerve (MS-BAN) activity were studied in an in vitro bladder-pelvic afferent nerve preparation. MS-BAN activity was induced by isotonic distention of the bladder at pressures of 10-40 cmH2O. The effect of epibatidine varied according to the concentration, route of administration and the intravesical pressure stimulus. Epibatidine (300-500 nM) administered in the perfusate to the serosal surface of the bladder decreased distension evoked afferent firing by 30-50% depending on the bladder pressure. However these concentrations also produced an immediate increase in tonic afferent firing in the empty bladder. Lower concentrations (50-100 nM) elicited weaker and more variable effects. The inhibitory effects were blocked by bath application of mecamylamine (150 µM) a nicotinic receptor antagonist. Bath application of nicotine (20 µM) elicited similar effects. Intravesical administration of epibatidine (500 nM) significantly increased MS-BAN firing by 15-30%; while lower concentrations (200-300 nM) were ineffective. This facilitatory effect of epibatidine was blocked by intravesical administration of mecamylamine (250 µM). Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Bath application of epibatidine (300 nM) or nicotine (20 µM) did not change either the voltage threshold or the area of evoked AP. These results indicate that nicotinic agonists: (1) enhance MS-BAN activity originating at afferent receptors near the urothelium, (2) inhibit MS-BAN activity originating at afferent receptors located at other sites in the bladder, (3) directly excite unidentified afferents, (4) do not alter afferent axonal excitability.

Keywords: Bladder afferent nerves; Epibatidine; Neuronal nicotinic receptors; Nicotine; Urothelium.