Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT(3A(b)) expressed in Xenopus laevis oocytes

Ian D. Mair, Jeremy J. Lambert, Jay Yang, John Dempster, John A. Peters

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

1. The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit ((5-HT(3A(b)) heterologously expressed in Xenopus laevis oocytes. 2. at negative holding potentials, bath applied 5-HT (300 nM-10 μM) evoked a transient, concentration-dependent (EC50 = 1.1 ± 0.1 μM). inward current. The response reversed in sign at a holding potential of -2.1 ± 1.6 mV. 3. The response to 5-HT was mimicked by the 5-HT, receptor selective agonists 2-methyl-5-HT (EC50 = 4.1 ± 0.2 μM), 1-phenylbiguanide (EC50 = 3.0 ± 0.1 μM), 3-chlorophenylbiguanide (EC50 = 140 ± 10 nM, 3,5-dichlorophenylbiguanide (EC50 = 14.5 ± 0.4 nM) and 2,5-dichlorophenylbiguanide (EC50 = 10.2 ± 0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 μM) of 5-HT. 4. Responses evoked by 5-HT at EC50 were blocked by the 5-HT3 receptor selective antagonist ondansetron (IC50 = 231 ± 22 pM) and by the less selective agents (+)-tubocurarine (IC50 = 31.9 ± 0.01 nM) and cocaine (IC50 = 2.1 ± 0.2 μM). 5. The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT(3A) subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT3 receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT(3A) subunit orthologues.

Original languageEnglish
Pages (from-to)1667-1674
Number of pages8
JournalBritish Journal of Pharmacology
Volume124
Issue number8
DOIs
Publication statusPublished - Aug 1998

Keywords

  • (+)-tubocurarine
  • 2-methyl-5-HT
  • 5-HT(3A) receptor subunit
  • 5-HT receptor
  • 5-hydroxytryptamine (5-HT)
  • Arylbiguanides
  • Cocaine
  • Ondansetron

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