Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle

The smooth muscle cells of the urinary tract are again the subject of much study, as is reflected by the papers in this section. Authors from Sheffield evaluate the effects of 5-HT on the potentiation of cholinergic responses in isolated strips of detrusor muscle. In another study authors from France compare the effects of tamsulosin and alfuzosin on neurally evoked increases of bladder neck and seminal vesicle pressures in rats. The smooth muscle of the renal artery is assessed by authors from Germany, where they investigate the involvement of signal-transducing GTP-binding proteins in renal artery smooth muscle contraction. To compare the serotonin (5-HT)(4)-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 mumol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pK(B) values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. These results indicate that 5-HT4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.