Variable Participation of 5-HT1-Like Receptors and 5-HT2 Receptors in Serotonin-Induced Contraction of Human Isolated Coronary Arteries

Background Serotonin 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-HT1D receptor subtypes, 5-HT'1D, and 5 -HT1Ds. Although these subtypes have similar pharmacology, 5-HT1Dg receptors appear to have lower affinity for ketanserin than 5-HT1Di receptors. We assessed the relative participation of 5-HT1-like and 5-HT2 receptors and attempted to identify whether vasoconstrictor 5-HT1-like receptors are 5 1HTDa or 5-.HIlD . Methods and Results Epicardial coronary arteries were dissected from the hearts of 29 patients (including 1 healthy donor) undergoing heart transplant operation. Endotheliumdenuded strips were set up to contract at 37°C. To assess the relative contributions of 5-HT,-like and 5-HT2 receptors, we blocked the latter with ketanserin (0.1 to 1.0 ,umol/L) and ketanserin-resistant receptors with methiothepin (0.1 ymol/ 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 -HT2 receptors to the maximum effect of 5 -HT, fl and f2,