BackgroundSerotonin may contract human large coronary arteries through two 5-hydroxtryptamine (5-HT) receptors, 5-HT1-like and 5 -HT2.These 5-HT1-like receptors resemble both cloned 5-HT1Dreceptor subtypes, 5-HT1Dαand 5 -HT1DβAlthough these subtypes have similar pharmacology, 5-HT1Dαreceptors appear to have lower affinity for ketanserin than 5-HT1Dαreceptors. We assessed the relative participation of 5-HT1-like and 5-HT2receptors and attempted to identify whether vasoconstrictor 5-HT1-like receptors are 5 1HT1Dαor 5-.HT1Dβ.Methods and ResultsEpicardial coronary arteries were dissected from the hearts of29 patients (including 1 healthy donor) undergoing heart transplant operation. Endothelium-denuded strips were set up to contract at 37°C. To assess the relative contributions of 5-HT2-like and 5-HT2receptors, we blocked the latter with ketanserin (0.1 to 1.0 μmol/L) and ketanserin-resistant receptors with methiothepin (0.1 μmol/ L). Concentration-effect curves for 5-HT, in the absence and presence of ketanserin, were analyzed by using a model for two receptor subtypes. The fractional contributions of 5-HT1-like and 5 -HT2receptors to the maximum effect of 5 -HT, f1and f2, were estimated in arteries from 28 patients: f1(0.71±0.20, mean±SD) was significantly larger than f2(0.29±0.20) (P<.0001). Using [3H]-serotonin to label transfected and ex-pressed receptors, we verified that ketanserin has lower affinity for 5-HT1Dβ(pK1-log Ki, mol/L] less than 5.0) than for 5-HTlDα(pKi=7.1±0.1) receptors. A concentration of ketanserin (1 μmol/L) that would occupy more than 90% of 5-HT1Dαreceptors failed to block 5-HT-induced contractions (4 patients). The 5-HT1-like receptor stimulant sumatriptan evoked maximal contractions that matched f1and was equipotent with 5-HT through 5-HT1-like receptors (8 patients). No systematic influence of disease, atheroma, or therapy on f1and f2was detected.ConclusionsCoronary artery contractile 5-HT1-like receptors resemble cloned 5-HT1Dβreceptors and predominate over 5-HT2receptors in mediating serotonin-evoked contractions. Sumatriptan contracts coronary arteries as a full agonist through 5-HT1-like receptors.