Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes

D. L. Downie, A. G. Hope, J. J. Lambert, J. A. Peters, T. P. Blackburn, B. J. Jones

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The actions of 5-hydroxytryptamine3 (5-HT3) receptor agonists and antagonists have been determined on the recombinant murine 5-HT3 R-A and an apparent splice variant of this subunit, termed 5-HT3 R-As. When expressed in Xenopus laevis oocytes, both forms of the subunit functioned as a homo-oligomeric complex and exhibited inward current responses to bath applied 5-HT. Analysis of the 5-HT concentration-response curve obtained with either homo-oligomer gave Hill coefficients greater than two, suggesting positive co-operativity within the receptor complex. The rank order of potency of a range of 5-HT3 receptor agonists [m-chlorophenylbiguanide > 5-HT > 2-methyl-5-HT (2-Me-5-HT) ≥ phenylbiguanide] was identical for both subunits. Indeed, with the exception of 2-Me-5-HT, for the agonists tested there was little difference across the subunits in either their potency, or the maximal current response that they elicited relative to 5-HT. Although 2-Me-5-HT exhibited a similar potency for both subunits, the maximal response evoked by this agonist at the 5-HT3 R-As subunit was much reduced when compared to the 5-HT3 R-A subunit. The 5-HT-induced current mediated by either form of the subunit was inhibited by the 5-HT3 receptor selective antagonists BRL 46470, granisetron and ondansetron and the non-selective antagonists (+)-tubocurarine, metoclopramide and cocaine in a reversible and concentration-dependent manner. These antagonists did not discriminate between the subunits and their potencies were similar to those reported previously for 5-HT3 receptors native to murine neuronal cells. These results are discussed in terms of a possible diversity of 5-HT3 receptors within a species.

Original languageEnglish
Pages (from-to)473-482
Number of pages10
JournalNeuropharmacology
Volume33
Issue number3-4
DOIs
Publication statusPublished - Mar 1994

Fingerprint

Xenopus laevis
Oocytes
Serotonin
Pharmacology
Granisetron
Ondansetron
Tubocurarine
Serotonin Receptor Agonists
Metoclopramide
Baths
Cocaine

Keywords

  • 5-HT
  • 5-HT receptor
  • 5-HT receptor agonists
  • 5-HT receptor antagonists
  • Ligand-gated ion channel

Cite this

@article{04d182531dbb4f8c9b470cfece67247a,
title = "Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes",
abstract = "The actions of 5-hydroxytryptamine3 (5-HT3) receptor agonists and antagonists have been determined on the recombinant murine 5-HT3 R-A and an apparent splice variant of this subunit, termed 5-HT3 R-As. When expressed in Xenopus laevis oocytes, both forms of the subunit functioned as a homo-oligomeric complex and exhibited inward current responses to bath applied 5-HT. Analysis of the 5-HT concentration-response curve obtained with either homo-oligomer gave Hill coefficients greater than two, suggesting positive co-operativity within the receptor complex. The rank order of potency of a range of 5-HT3 receptor agonists [m-chlorophenylbiguanide > 5-HT > 2-methyl-5-HT (2-Me-5-HT) ≥ phenylbiguanide] was identical for both subunits. Indeed, with the exception of 2-Me-5-HT, for the agonists tested there was little difference across the subunits in either their potency, or the maximal current response that they elicited relative to 5-HT. Although 2-Me-5-HT exhibited a similar potency for both subunits, the maximal response evoked by this agonist at the 5-HT3 R-As subunit was much reduced when compared to the 5-HT3 R-A subunit. The 5-HT-induced current mediated by either form of the subunit was inhibited by the 5-HT3 receptor selective antagonists BRL 46470, granisetron and ondansetron and the non-selective antagonists (+)-tubocurarine, metoclopramide and cocaine in a reversible and concentration-dependent manner. These antagonists did not discriminate between the subunits and their potencies were similar to those reported previously for 5-HT3 receptors native to murine neuronal cells. These results are discussed in terms of a possible diversity of 5-HT3 receptors within a species.",
keywords = "5-HT, 5-HT receptor, 5-HT receptor agonists, 5-HT receptor antagonists, Ligand-gated ion channel",
author = "Downie, {D. L.} and Hope, {A. G.} and Lambert, {J. J.} and Peters, {J. A.} and Blackburn, {T. P.} and Jones, {B. J.}",
year = "1994",
month = "3",
doi = "10.1016/0028-3908(94)90078-7",
language = "English",
volume = "33",
pages = "473--482",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier",
number = "3-4",

}

Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes. / Downie, D. L.; Hope, A. G.; Lambert, J. J.; Peters, J. A.; Blackburn, T. P.; Jones, B. J.

In: Neuropharmacology, Vol. 33, No. 3-4, 03.1994, p. 473-482.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes

AU - Downie, D. L.

AU - Hope, A. G.

AU - Lambert, J. J.

AU - Peters, J. A.

AU - Blackburn, T. P.

AU - Jones, B. J.

PY - 1994/3

Y1 - 1994/3

N2 - The actions of 5-hydroxytryptamine3 (5-HT3) receptor agonists and antagonists have been determined on the recombinant murine 5-HT3 R-A and an apparent splice variant of this subunit, termed 5-HT3 R-As. When expressed in Xenopus laevis oocytes, both forms of the subunit functioned as a homo-oligomeric complex and exhibited inward current responses to bath applied 5-HT. Analysis of the 5-HT concentration-response curve obtained with either homo-oligomer gave Hill coefficients greater than two, suggesting positive co-operativity within the receptor complex. The rank order of potency of a range of 5-HT3 receptor agonists [m-chlorophenylbiguanide > 5-HT > 2-methyl-5-HT (2-Me-5-HT) ≥ phenylbiguanide] was identical for both subunits. Indeed, with the exception of 2-Me-5-HT, for the agonists tested there was little difference across the subunits in either their potency, or the maximal current response that they elicited relative to 5-HT. Although 2-Me-5-HT exhibited a similar potency for both subunits, the maximal response evoked by this agonist at the 5-HT3 R-As subunit was much reduced when compared to the 5-HT3 R-A subunit. The 5-HT-induced current mediated by either form of the subunit was inhibited by the 5-HT3 receptor selective antagonists BRL 46470, granisetron and ondansetron and the non-selective antagonists (+)-tubocurarine, metoclopramide and cocaine in a reversible and concentration-dependent manner. These antagonists did not discriminate between the subunits and their potencies were similar to those reported previously for 5-HT3 receptors native to murine neuronal cells. These results are discussed in terms of a possible diversity of 5-HT3 receptors within a species.

AB - The actions of 5-hydroxytryptamine3 (5-HT3) receptor agonists and antagonists have been determined on the recombinant murine 5-HT3 R-A and an apparent splice variant of this subunit, termed 5-HT3 R-As. When expressed in Xenopus laevis oocytes, both forms of the subunit functioned as a homo-oligomeric complex and exhibited inward current responses to bath applied 5-HT. Analysis of the 5-HT concentration-response curve obtained with either homo-oligomer gave Hill coefficients greater than two, suggesting positive co-operativity within the receptor complex. The rank order of potency of a range of 5-HT3 receptor agonists [m-chlorophenylbiguanide > 5-HT > 2-methyl-5-HT (2-Me-5-HT) ≥ phenylbiguanide] was identical for both subunits. Indeed, with the exception of 2-Me-5-HT, for the agonists tested there was little difference across the subunits in either their potency, or the maximal current response that they elicited relative to 5-HT. Although 2-Me-5-HT exhibited a similar potency for both subunits, the maximal response evoked by this agonist at the 5-HT3 R-As subunit was much reduced when compared to the 5-HT3 R-A subunit. The 5-HT-induced current mediated by either form of the subunit was inhibited by the 5-HT3 receptor selective antagonists BRL 46470, granisetron and ondansetron and the non-selective antagonists (+)-tubocurarine, metoclopramide and cocaine in a reversible and concentration-dependent manner. These antagonists did not discriminate between the subunits and their potencies were similar to those reported previously for 5-HT3 receptors native to murine neuronal cells. These results are discussed in terms of a possible diversity of 5-HT3 receptors within a species.

KW - 5-HT

KW - 5-HT receptor

KW - 5-HT receptor agonists

KW - 5-HT receptor antagonists

KW - Ligand-gated ion channel

UR - http://www.scopus.com/inward/record.url?scp=0028237445&partnerID=8YFLogxK

U2 - 10.1016/0028-3908(94)90078-7

DO - 10.1016/0028-3908(94)90078-7

M3 - Article

C2 - 7984286

AN - SCOPUS:0028237445

VL - 33

SP - 473

EP - 482

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 3-4

ER -