TY - JOUR
T1 - 5-Hydroxytryptamine interaction with the nicotinic acetylcholine receptor
AU - Blanton, Michael P.
AU - McCardy, Elizabeth A.
AU - Fryer, John D.
AU - Liu, Minghua
AU - Lukas, Ronald J.
N1 - Funding Information:
This research was supported in part by National Institutes of Health NINDS Grant R29 NS35786. Studies done in Phoenix were supported by the Barrow Neurological Foundation and the Arizona Disease Control Research Commission (grants 82-1-098 and 9730 to RJL). The contents of this report are solely the responsibility of the authors and do not necessarily represent the views of the aforementioned awarding agencies.
PY - 2000/2/18
Y1 - 2000/2/18
N2 - 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.
AB - 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.
KW - 5-HT (5- hydroxytryptamine, serotonin)
KW - Antagonist
KW - Competitive
KW - Nicotinic acetylcholine receptor
KW - Noncompetitive
KW - Photoaffinity labeling
UR - http://www.scopus.com/inward/record.url?scp=0034681405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034681405&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00855-9
DO - 10.1016/S0014-2999(99)00855-9
M3 - Article
C2 - 10688979
AN - SCOPUS:0034681405
SN - 0014-2999
VL - 389
SP - 155
EP - 163
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -