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-HT(3)Rs 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 alpha 7 activation. These results confirm the notion of families of receptors and further indicate that strong similarities can exist in some critical binding domains. (C) 1998 Elsevier Science Ireland Ltd.