The present study examines the interaction of the neurotransmitter 5- hydroxytryptamine (5-HT) with muscle-type nicotinic acetylcholine receptors. 5-HT inhibits the initial rate of [125I]α-bungarotoxin binding to Torpedo acetylcholine receptor membranes (IC50=8.5±0.32 mM) and [3H]5-HT can be photoincorporated into acetylcholine receptor subunits, with labeling of the α-subunit inhibitable by both agonists and competitive antagonists. Within the agonist-binding domain, [3H]5-HT photoincorporates into αTyr190, αCys192 and αCys193. Functional studies using the human clonal cell line TE671/RD, show that 5-HT is a weak inhibitor (IC50=1.55±0.25 mM) of acetylcholine receptor activity. In this regard, agonist-response profiles in the absence and presence of 5-HT indicate a noncompetitive mode of inhibition. In addition, 5-HT displaces high affinity [3H]thienylcyclohexylpiperidine binding to the desensitized Torpedo acetylcholine receptor channel (IC50=1.61±0.07 mM). Collectively, these results indicate that 5-HT interacts weakly with the agonist recognition site and inhibits receptor function noncompetitively by binding to the acetylcholine receptor channel. (C) 2000 Elsevier Science B.V.
- 5-HT (5- hydroxytryptamine, serotonin)
- Nicotinic acetylcholine receptor
- Photoaffinity labeling
ASJC Scopus subject areas