Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes

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Abstract

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 α-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 α7 activation. These results confirm the notion of families of receptors and further indicate that strong similarities can exist in some critical binding domains.

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Acknowledgements

The authors gratefully acknowledge the generous gift of the cloned mouse 5-HT3R from Dr. David Julius (University of California, San Francisco, CA, USA). The preparation of cRNA by Stefan Luhowskyj is also gratefully acknowledged, as is the synthesis of compounds by Dr. Michael Balestra and Chris Becker. We would also like to thank Dr. Jack Gordon for his support and valuable discussions.

References (24)

  • T. Akasu et al.

    Modulation of the sensitivity of nicotinic receptors in autonomic ganglia

    Experientia

    (1989)
  • J.-P. Changeux et al.

    The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis

    Q. Rev. Biophys.

    (1992)
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