Antagonism of thromboxane receptor induced contractions in isolated human groin lymphatics

In vitro studies were performed on lymphatics obtained from the groin in 19 patients undergoing vascular surgery. The lymphatics were mounted in tissue baths, and isometric contractions were induced by increasing concentrations of the thromboxane A2 (TXA2) mimetic U-46619. In comparison to K+ (124mM)-induced contraction, which were used as an internal standard, the response to U-46619 had an Emax of 105 +/- 5.9%. The pEC50-value was 8.14 +/- 0.09. The effects of two thromboxane receptor (TP-receptor) antagonists, L-636,499 and BM-13,505, were investigated. Both antagonists caused concentration-dependent right-ward shifts without depression of Emax of the U-46619 concentration-response curves. The slopes of the regression lines in a Schild plot for both antagonists did not differ from one, indicating competitive antagonism. The pA2-value of BM-13,505 (7.89) was 65 times higher than that of L-636,499 (6.08). The results suggest that the receptor involved in the prostanoid contraction in human groin lymphatics is of the TP-subtype.