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

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-HT1 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-HT1D/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.