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5-Hydroxytryptamine inhibits P2X2 receptor channel pore mutants

K Nakazawa1, Y Ohno

  • 1Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan. nakazawa@nihs.go.jp

Cellular and Molecular Neurobiology
|June 29, 1999
PubMed

Insights

5-Hydroxytryptamine enhances wild-type P2X2 receptor/channel currents but inhibits mutants. This suggests 5-hydroxytryptamine binds to the P2X2 receptor/channel pore, particularly at Thr330 and Asn333 residues.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • The P2X2 receptor is an ATP-gated ion channel involved in neurotransmission.
  • 5-Hydroxytryptamine (serotonin) is a key neurotransmitter with diverse physiological roles.

Purpose of the Study:

  • To investigate the interaction of 5-hydroxytryptamine with the P2X2 receptor/channel.
  • To elucidate the specific binding sites and mechanisms of 5-hydroxytryptamine modulation on P2X2 receptor activity.

Main Methods:

  • Utilized Xenopus oocytes for expressing wild-type and mutant P2X2 receptor/channels.
  • Employed electrophysiological techniques to measure ionic currents mediated by P2X2 receptors.
  • Investigated the effects of 5-hydroxytryptamine (10 microM) on receptor activity.

Main Results:

  • 5-Hydroxytryptamine (10 microM) enhanced ionic current through wild-type P2X2 receptors.
  • 5-Hydroxytryptamine (10 microM) inhibited currents in P2X2 receptor mutants T330I and N333I.
  • Mutations neutralizing Thr330 or Asn333 revealed a high-affinity inhibitory binding site for 5-hydroxytryptamine.

Conclusions:

  • The findings suggest that 5-hydroxytryptamine interacts with the P2X2 receptor/channel at the channel pore.
  • Neutralization of Thr330 or Asn333 residues is critical for the inhibitory action of 5-hydroxytryptamine.
  • This implies a specific interaction site within the pore for 5-hydroxytryptamine binding.

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