Evidence for the presynaptic action of 5-hydroxytryptamine and the involvement of purinergic innervation in the rabbit lower urinary tract.

1. The effects of 5-hydroxytryptamine (5-HT) were studied in vitro on bladder and urethral muscle strips from the rabbit. 5-HT produced dose-dependent contraction in the detrusor and urethra. 2. The 5-HT-induced contraction could be dose-dependently inhibited by the 5-HT3 antagonists MDL 72222, ICS 205-930 and BRL 43694. No effect of ketanserin, methysergide or metitepine was observed on the contractile response to 5-HT. 3. Atropine and alpha, beta-methylene ATP both partially blocked the contractile response to 5-HT. Together they caused more inhibition than either alone. 4. Atropine and alpha, beta-methylene ATP also inhibited the contractile response to electrical field stimulation. The 5-HT3 antagonist MDL 72222 had no effect on the contraction to field stimulation. 5. The atropine- and alpha, beta-methylene ATP-resistant components of 5-HT-induced contraction were not affected by the 5-HT1 antagonists metitepine, the 5-HT2 antagonists ketanserin and methysergide or the 5-HT3 antagonists MDL 72222, ICS 205-930 and BRL 43694. 6. Tetrodotoxin, hexamethonium, phentolamine and prazosin had no effect on the contractile response to 5-HT. 7. These results suggest that in the rabbit lower urinary tract (i) there are 5-HT3 receptors, (ii) the contractile response to 5-HT is mediated by presynaptic stimulation, (iii) there is non-adrenergic, non-cholinergic excitatory neurotransmission.