Involvement of non-classical 5-HT receptor in serotonin and cisapride induced secretion in hen colon

1. In hen colon 5-HT induces a tetrodotoxin-resistant, bumetanide-sensitive, chloride secretion, positively coupled with adenylate cyclase activity. 2. The 5-HT receptor mediating this response seems non-classical since it cannot be blocked by 5-HT1-like, 5-HT2 or 5-HT3 antagonists. 3. Effects are presented of new putative 5-HT agonists and antagonists on short circuit current and cord conductance in the hen colon, using the Ussing chamber technique. 4. The substituted benzamides, cisapride and BRL 24924, induced a dose-dependent short circuit currents but both with less potency than 5-HT. 5. Cisapride mediated this dose-dependent bumetanide sensitive response mainly by release of acetylcholine, since atropine reduced cisapride response by 70%. 6. Neither BRL 24924, 5-HTP-DP, ketanserin, ICS 205-930, prazosin, yohimbine, atropine nor piroxicam, covering the 5-HT1P, 5-HT2P, 5-HT2, 5-HT3, 5-HT4, adrenergic and muscarinic receptor types and the prostaglandin synthesis, altered 5-HT induced increases in short circuit current and cord conductance. 7. Results suggest (a) cisapride mediates it's response mainly by releasing acetylcholine, which then stimulates muscarinic receptors to release 5-HT. (b) Involvement of a non-classical 5-HT receptor subtype in 5-HT induced chloride secretion in hen colon.