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.
Chen
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University Department of Pharmacology, University of Oxford.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D017829:Granisetron; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011687:Purines / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron; D014521:Urethra / Q000187:drug effects; D014551:Urinary Tract / Q000294:innervation*
D000255:Adenosine Triphosphate; D001285:Atropine; D017829:Granisetron; D007191:Indazoles; D007211:Indoles; D011687:Purines; D012701:Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D000077526:Tropisetron; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C042253:bemesetron