5-Hydroxytryptamine Receptor Subtpes in Human Coronary Arteries

Background. Platelets release two powerful vasoconstrictors thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT). Animal studies have suggested that these two substances may act in a synergistic fashion to stimulate platelet activity and smooth muscle vasoconstriction. Methods and Results. To assess the interaction between TXA2 and 5-HT at the individual 5--HT receptor subtypes reported to mediate contraction, the effect of the amine was determined in the presence of differing concentrations of the thromboxane mimetic U46619. A total of 168 vessel segments were removed from 20 recipient hearts of patients undergoing cardiac transplantation. Segments were set up in isolated organ baths and tested for their response to 5-HT in the presence of an EC1,( EC30, or EC_% concentration of U46619 (n=4). A synergistic response was only seen in a small number of the segments tested under these conditions. However, in the presence of ketanserin (10-6 M) to block 5-HT2 receptors, there was a significant increase in the response to 10-6 M 5--HT in the presence of both the EC30 (p<0.025) and EC5 (p<0.0S) concentrations of U46619 (n=4). The potentiation of non-S-HT2 receptor mediated responses to 5-HT, in the presence of U46619 (EC30), could be prevented by 10-7 M methiothepin, a nonselective 5-HT1-like/5-HT2 receptor antagonist. Conclusions. These data indicate that TXA2 receptor activation can increase the response of 5-HT mediated by 5-HT1-like receptors in human coronary arteries. 5-HTI-like receptors have been shown to mediate the contractile effect of 5-HT in patients with variant and chronic stable angina. Thus, platelet contents may act together at specific receptor subtypes in the induction of myocardial ischemia. (Circulation 1993;87:874-880)