Pharmacological properties of serotonin receptor subtypes mediating contraction of bovine inferior alveolar arteries

H. A. O'Donohue, Peter W. Abel, Charles Bockman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes mediating contraction of the inferior alveolar artery. Additionally, to determine the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT. Methods: Contractile responses to 5-HT were examined in vitro using ring segments of bovine inferior alveolar arteries. Affinity constants (KB's) of subtype-selective 5-HT receptor antagonists were determined to characterise the 5-HT receptor-subtypes causing contraction of inferior alveolar arteries. Results: In 100nM ketanserin or 30nM spiperone, 5-HT caused a biphasic contraction best-fit by a two-site curve model, where one site was antagonist-sensitive and the other site antagonist-insensitive. 5-HT2A receptor-subtype selective antagonists, ketanserin and spiperone, blocked 5-HT induced contraction with KB's of 1.0 and 0.16nM, respectively. RS102221 (5-HT2C selective) and (S)-WAY100135 (5-HT1A selective) blocked 5-HT stimulated contraction with low affinities (KB's=100nM and 330nM, respectively). GR55562, a 5-HT 1 receptor subtype antagonist with a reported affinity of 500nM at the 5-HT1D receptor subtype, blocked 5-HT induced contraction with a KB of 470nM. Cylooxygenase inhibition with 50μM ibuprofen caused a 44% increase in maximal contraction to 5-HT; whereas, nitric oxide inhibition with NG-nitro-L-arginine, endothelium removal or inhibition of 5-HT uptake and monoamine oxidase with imipramine and iproniazid, respectively, did not affect 5-HT contraction. Conclusions: Both 5-HT2A and 5-HT 1D/1B receptor subtypes mediate 5-HT induced contraction of the bovine inferior alveolar artery. 5-HT stimulated contraction of the inferior alveolar artery is modulated by a vasodilator prostaglandin.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalArchives of Oral Biology
Volume49
Issue number3
DOIs
StatePublished - Mar 2004

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Serotonin Receptors
Serotonin
Arteries
Pharmacology
Spiperone
Ketanserin
Monoamine Oxidase
Endothelium
Nitric Oxide
Receptor, Serotonin, 5-HT1D
Iproniazid
Receptor, Serotonin, 5-HT1B
Receptor, Serotonin, 5-HT2A
Serotonin Antagonists
Imipramine
Nitroarginine
Ibuprofen
Prostaglandin-Endoperoxide Synthases
Vasodilator Agents
Prostaglandins

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

@article{dcd23adb205445e69db5f7149c208f76,
title = "Pharmacological properties of serotonin receptor subtypes mediating contraction of bovine inferior alveolar arteries",
abstract = "Objective: To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes mediating contraction of the inferior alveolar artery. Additionally, to determine the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT. Methods: Contractile responses to 5-HT were examined in vitro using ring segments of bovine inferior alveolar arteries. Affinity constants (KB's) of subtype-selective 5-HT receptor antagonists were determined to characterise the 5-HT receptor-subtypes causing contraction of inferior alveolar arteries. Results: In 100nM ketanserin or 30nM spiperone, 5-HT caused a biphasic contraction best-fit by a two-site curve model, where one site was antagonist-sensitive and the other site antagonist-insensitive. 5-HT2A receptor-subtype selective antagonists, ketanserin and spiperone, blocked 5-HT induced contraction with KB's of 1.0 and 0.16nM, respectively. RS102221 (5-HT2C selective) and (S)-WAY100135 (5-HT1A selective) blocked 5-HT stimulated contraction with low affinities (KB's=100nM and 330nM, respectively). GR55562, a 5-HT 1 receptor subtype antagonist with a reported affinity of 500nM at the 5-HT1D receptor subtype, blocked 5-HT induced contraction with a KB of 470nM. Cylooxygenase inhibition with 50μM ibuprofen caused a 44{\%} increase in maximal contraction to 5-HT; whereas, nitric oxide inhibition with NG-nitro-L-arginine, endothelium removal or inhibition of 5-HT uptake and monoamine oxidase with imipramine and iproniazid, respectively, did not affect 5-HT contraction. Conclusions: Both 5-HT2A and 5-HT 1D/1B receptor subtypes mediate 5-HT induced contraction of the bovine inferior alveolar artery. 5-HT stimulated contraction of the inferior alveolar artery is modulated by a vasodilator prostaglandin.",
author = "O'Donohue, {H. A.} and Abel, {Peter W.} and Charles Bockman",
year = "2004",
month = "3",
doi = "10.1016/j.archoralbio.2003.09.003",
language = "English",
volume = "49",
pages = "223--232",
journal = "Archives of Oral Biology",
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T1 - Pharmacological properties of serotonin receptor subtypes mediating contraction of bovine inferior alveolar arteries

AU - O'Donohue, H. A.

AU - Abel, Peter W.

AU - Bockman, Charles

PY - 2004/3

Y1 - 2004/3

N2 - Objective: To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes mediating contraction of the inferior alveolar artery. Additionally, to determine the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT. Methods: Contractile responses to 5-HT were examined in vitro using ring segments of bovine inferior alveolar arteries. Affinity constants (KB's) of subtype-selective 5-HT receptor antagonists were determined to characterise the 5-HT receptor-subtypes causing contraction of inferior alveolar arteries. Results: In 100nM ketanserin or 30nM spiperone, 5-HT caused a biphasic contraction best-fit by a two-site curve model, where one site was antagonist-sensitive and the other site antagonist-insensitive. 5-HT2A receptor-subtype selective antagonists, ketanserin and spiperone, blocked 5-HT induced contraction with KB's of 1.0 and 0.16nM, respectively. RS102221 (5-HT2C selective) and (S)-WAY100135 (5-HT1A selective) blocked 5-HT stimulated contraction with low affinities (KB's=100nM and 330nM, respectively). GR55562, a 5-HT 1 receptor subtype antagonist with a reported affinity of 500nM at the 5-HT1D receptor subtype, blocked 5-HT induced contraction with a KB of 470nM. Cylooxygenase inhibition with 50μM ibuprofen caused a 44% increase in maximal contraction to 5-HT; whereas, nitric oxide inhibition with NG-nitro-L-arginine, endothelium removal or inhibition of 5-HT uptake and monoamine oxidase with imipramine and iproniazid, respectively, did not affect 5-HT contraction. Conclusions: Both 5-HT2A and 5-HT 1D/1B receptor subtypes mediate 5-HT induced contraction of the bovine inferior alveolar artery. 5-HT stimulated contraction of the inferior alveolar artery is modulated by a vasodilator prostaglandin.

AB - Objective: To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes mediating contraction of the inferior alveolar artery. Additionally, to determine the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT. Methods: Contractile responses to 5-HT were examined in vitro using ring segments of bovine inferior alveolar arteries. Affinity constants (KB's) of subtype-selective 5-HT receptor antagonists were determined to characterise the 5-HT receptor-subtypes causing contraction of inferior alveolar arteries. Results: In 100nM ketanserin or 30nM spiperone, 5-HT caused a biphasic contraction best-fit by a two-site curve model, where one site was antagonist-sensitive and the other site antagonist-insensitive. 5-HT2A receptor-subtype selective antagonists, ketanserin and spiperone, blocked 5-HT induced contraction with KB's of 1.0 and 0.16nM, respectively. RS102221 (5-HT2C selective) and (S)-WAY100135 (5-HT1A selective) blocked 5-HT stimulated contraction with low affinities (KB's=100nM and 330nM, respectively). GR55562, a 5-HT 1 receptor subtype antagonist with a reported affinity of 500nM at the 5-HT1D receptor subtype, blocked 5-HT induced contraction with a KB of 470nM. Cylooxygenase inhibition with 50μM ibuprofen caused a 44% increase in maximal contraction to 5-HT; whereas, nitric oxide inhibition with NG-nitro-L-arginine, endothelium removal or inhibition of 5-HT uptake and monoamine oxidase with imipramine and iproniazid, respectively, did not affect 5-HT contraction. Conclusions: Both 5-HT2A and 5-HT 1D/1B receptor subtypes mediate 5-HT induced contraction of the bovine inferior alveolar artery. 5-HT stimulated contraction of the inferior alveolar artery is modulated by a vasodilator prostaglandin.

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