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5‐Hydroxytryptamine‐induced potentiation of cholinergic responses to electrical field stimulation in pig detrusor muscle
Author(s) -
Sellers D.J.,
ChessWilliams R.,
Chapple C.R.
Publication year - 2000
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2000.00868.x
Subject(s) - cholinergic , stimulation , endocrinology , agonist , medicine , receptor , 5 ht receptor , detrusor muscle , carbachol , long term potentiation , chemistry , serotonin , pharmacology , biology , smooth 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 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 µmol/L) were constructed in the presence and absence of the 5‐HT 4 ‐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‐HT 1 , ‐HT 2 and ‐HT 3 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). BothRS‐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‐HT 4 receptor subtype. Conclusion These data indicate that 5‐HT can potentiate EFS responses in isolated pig bladder strips and that the 5‐HT 4 receptor subtype mediates this response. Therefore, the pig may be used as an effective model to study presynaptic 5‐HT 4 receptors previously reported in the human bladder.