Interaction between thromboxane A2 and 5-hydroxytryptamine receptor subtypes 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.


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 EC10, EC30, or EC50 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 EC50 (p < 0.05) concentrations of U46619 (n = 4). The potentiation of non-5-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-HT1-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.
Chester
A H
AH
National Heart and Lung Institute, Harefield Hospital, Middlesex, UK.
Allen
S P
SP
Tadjkarimi
S
S
Yacoub
M H
MH
D000328:Adult; D001158:Arteries; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008171:Lung Diseases / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000145:classification / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction
D011450:Prostaglandin Endoperoxides, Synthetic; D011985:Receptors, Serotonin; D017482:Receptors, Thromboxane; D012702:Serotonin Antagonists; D012701:Serotonin; D011189:Potassium Chloride; D007650:Ketanserin