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

Fingerprint

Serotonin Receptors
Xenopus laevis
Oocytes
Serotonin
Pharmacology
Inhibitory Concentration 50
Receptors, Serotonin, 5-HT3
Ondansetron
Tubocurarine
Serotonin Receptor Agonists
Patch-Clamp Techniques
Baths
Cocaine
Electrodes

Keywords

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

Cite this

@article{7ae66a09a22c40c5937d541d688fa655,
title = "Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT(3A(b)) expressed in Xenopus laevis oocytes",
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.",
keywords = "(+)-tubocurarine, 2-methyl-5-HT, 5-HT(3A) receptor subunit, 5-HT receptor, 5-hydroxytryptamine (5-HT), Arylbiguanides, Cocaine, Ondansetron",
author = "Mair, {Ian D.} and Lambert, {Jeremy J.} and Jay Yang and John Dempster and Peters, {John A.}",
year = "1998",
month = "8",
doi = "10.1038/sj.bjp.0702037",
language = "English",
volume = "124",
pages = "1667--1674",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",
number = "8",

}

Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT(3A(b)) expressed in Xenopus laevis oocytes. / Mair, Ian D.; Lambert, Jeremy J.; Yang, Jay; Dempster, John; Peters, John A.

In: British Journal of Pharmacology, Vol. 124, No. 8, 08.1998, p. 1667-1674.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT(3A(b)) expressed in Xenopus laevis oocytes

AU - Mair, Ian D.

AU - Lambert, Jeremy J.

AU - Yang, Jay

AU - Dempster, John

AU - Peters, John A.

PY - 1998/8

Y1 - 1998/8

N2 - 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.

AB - 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.

KW - (+)-tubocurarine

KW - 2-methyl-5-HT

KW - 5-HT(3A) receptor subunit

KW - 5-HT receptor

KW - 5-hydroxytryptamine (5-HT)

KW - Arylbiguanides

KW - Cocaine

KW - Ondansetron

U2 - 10.1038/sj.bjp.0702037

DO - 10.1038/sj.bjp.0702037

M3 - Article

C2 - 9756382

AN - SCOPUS:0031816512

VL - 124

SP - 1667

EP - 1674

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 8

ER -