Effect of the thromboxane A2-mimetic U46619 on 5-HT1-like and 5-HT2 receptor-mediated contraction of the rabbit isolated femoral artery.

1. The influence of the thromboxane A2-mimetic U46619 (11 alpha, 9 alpha-epoxymethano PGH2) on 5-hydroxy-tryptamine (5-HT)-induced contractions of the rabbit isolated femoral artery has been examined. 2. In the absence of U46619, 5-HT responses were mediated predominantly by 5-HT2-receptors as judged by potent, surmountable antagonism by the selective 5-HT2 receptor antagonists, spiperone and ketanserin. Both antagonists unmasked a population of 5-HT1-like receptors which accounted for approximately 10-15% of the 5-HT maximum response. 3. In the presence of U46619 (3-10 nM), 5-HT-induced contractions were largely resistant to blockade by 5-HT2 receptor antagonists since 5-HT1-like receptor-mediated contraction now accounted for approximately 60% of the 5-HT maximum response. 4. These results show that activation of thromboxane A2 receptors in a tissue possessing both 5-HT2 and 5-HT1-like receptors can convert 5-HT-induced contraction from one mediated predominantly by 5-HT2 receptors to one which is mediated predominantly by 5-HT1-like receptors.