5-hydroxytryptamine interaction with the nicotinic acetylcholine receptor.

M P Blanton, E A McCardy, J D Fryer, M Liu, R J Lukas

Department of Pharmacology, Texas Tech University, Health Sciences Center, 3601 4th Street, Lubbock, TX, USA. phrmpb@ttuhsc.edu

European journal of pharmacology 2000 Feb 18

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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]alpha-bungarotoxin binding to Torpedo acetylcholine receptor membranes (IC(50)=8.5+/-0.32 mM) and [3H]5-HT can be photoincorporated into acetylcholine receptor subunits, with labeling of the alpha-subunit inhibitable by both agonists and competitive antagonists. Within the agonist-binding domain, [3H]5-HT photoincorporates into alphaTyr(190), alphaCys(192) and alphaCys(193). Functional studies using the human clonal cell line TE671/RD, show that 5-HT is a weak inhibitor (IC(50)=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 (IC(50)=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.

Citation

M P Blanton, E A McCardy, J D Fryer, M Liu, R J Lukas. 5-hydroxytryptamine interaction with the nicotinic acetylcholine receptor. European journal of pharmacology. 2000 Feb 18;389(2-3):155-63