TY - JOUR
T1 - 5-hydroxytryptamine-induced potentiation of cholinergic responses to electrical field stimulation in pig detrusor
AU - Sellers, D. J.
AU - Chess-Williams, R.
AU - Chapple, C. R.
PY - 2000
Y1 - 2000
N2 - 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 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 lO0-s intervals and allowed to equilibrate. Concentration-response curves to 5-HT (1 nmol/L to 300 μmol/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 μmol/L) to block 5-HT1, -HT2 and -HT3 receptors. Results. 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. Conclusion. 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.
AB - 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 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 lO0-s intervals and allowed to equilibrate. Concentration-response curves to 5-HT (1 nmol/L to 300 μmol/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 μmol/L) to block 5-HT1, -HT2 and -HT3 receptors. Results. 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. Conclusion. 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.
UR - http://www.scopus.com/inward/record.url?scp=0033780711&partnerID=8YFLogxK
U2 - 10.1046/j.1464-410X.2000.00868.x
DO - 10.1046/j.1464-410X.2000.00868.x
M3 - Article
C2 - 11069383
AN - SCOPUS:0033780711
VL - 86
SP - 714
EP - 718
JO - British Journal of Urology
JF - British Journal of Urology
SN - 1464-410X
IS - 6
ER -