5-Hydroxytryptamine-induced potentiation of cholinergic responses to electrical field stimulation in pig detrusor muscle

Objective To determine whether detrusor muscle from the pig can be used as a model to study presynaptic 5-hydroxytryptamine (HT)(4)-receptor-mediated effects on the electrical field stimulated (EFS) cholinergic responses prev iously identified in the human bladder. Materials and methods Strips of detrusor muscle were mounted in physiologic al Krebs' solution under 1 g tension and field stimulated (25 Hz, 0.01 ms d uration, 60 V for 5 s) at 100-s intervals and allowed to equilibrate. Conce ntration-response curves to 5-HT (1 nmol/L to 300 mu mol/L) were constructe d in the presence and absence of the 5-HT4-selective antagonists RS-100235 and GR-113808 (both at 0.3, 1 and 3 nmol/L). All experiments were conducted in the presence of methiothepin and ondansetron (both 1 mu mol/L) to block 5-HT1, -HT2 and -HT3 receptors. Results 5-HT potentiated the cholinergic responses to EFS in pig bladder st rips in a concentration-dependent manner, with a maximum mean (SEM) potenti ation of 48.3 (7.7)% of the resting tension (n = 25). Both RS-100235 and GR -113808 antagonized the effect of 5-HT with high affinity, yielding apparen t pKB values which were consistent with the responses being mediated via th e 5-HT4 receptor subtype. Conclusion These data indicate that 5-HT can potentiate EFS responses in is olated pig bladder strips and that the 5-HT4 receptor subtype mediates this response. Therefore, the pig may be used as an effective model to study pr esynaptic 5-HT4 receptors previously reported in the human bladder.