Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes.
The 5-HT3 receptor (5-HT3R) is part of a superfamily of ligand-gated ion channels which includes nicotinic acetylcholine receptors (nAChR). cRNA derived from the long isoform cloned mouse 5-HT3R was used to drive expression of 5-HT3Rs in Xenopus oocytes. 5-HT-induced currents were monitored using two-electrode voltage-clamp. Eight nicotinic agonists, including ACh and nicotine, but not alpha-anatoxin, were found to antagonize 5-HT-induced currents. With the exception of 3-(2,4)-dimethoxybenzylidene-anabaseine (DMXB-anabaseine; GTS-21) this antagonism appeared to be competitive since it could be overcome by increasing concentrations of 5-HT. Potency of 5-HT3 antagonism was comparable to reported values for nAChR alpha7 activation. These results confirm the notion of families of receptors and further indicate that strong similarities can exist in some critical binding domains.
Gurley
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Astra Arcus USA, Rochester, NY 14534, USA. david.gurley@arcus.us.astra.com
Lanthorn
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D000087522:Cyanobacteria Toxins; D018076:DNA, Complementary / Q000235:genetics; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005260:Female; D008387:Marine Toxins / Q000494:pharmacology; D051379:Mice; D052998:Microcystins; D005810:Multigene Family; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry; D011985:Receptors, Serotonin / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D001427:Bacterial Toxins; D001597:Benzylidene Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000087522:Cyanobacteria Toxins; D018076:DNA, Complementary; D008387:Marine Toxins; D052998:Microcystins; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins; D012702:Serotonin Antagonists; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; C082748:epibatidine; D002794:Choline; D000109:Acetylcholine