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

Abstract

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 previously identified in the human bladder. Materials and methods Strips of detrusor muscle were mounted in physiological Krebs' solution under 1 g tension and field stimulated (25 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals and allowed to equilibrate. Concentration-response curves to 5-HT (1 nmol/L to 300 micromol/L) were constructed 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 micromol/L) to block 5-HT1, -HT2 and -HT3 receptors. 5-HT potentiated the cholinergic responses to EFS in pig bladder strips in a concentration-dependent manner, with a maximum mean (SEM) potentiation 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 apparent pKB values which were consistent with the responses being mediated via the 5-HT4 receptor subtype. These data indicate that 5-HT can potentiate EFS responses in isolated 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 presynaptic 5-HT4 receptors previously reported in the human bladder.