Effects of the thromboxane-receptor antagonist L-636,499 on feline cerebral arteries.

The effects of the thromboxane-receptor antagonist L-636,499 on contractions induced by U46619 and prostaglandin (PG)F2 alpha were studied in the isolated feline basilar artery (BA). L-636,499 (10(-6)-3 X 10(-5) mol l-1) shifted concentration-response curves induced by U46619 to the right in a parallel manner. By contrast, concentration-response curves induced by PGF2 alpha were displaced only when L-636,499 concentrations of 10(-5) and 3 X 10(-5) mol l-1 were used. The Schild plot using U46619 as the agonist revealed a slope index (0.69) which was significantly less than unity. PA2-values calculated according to the method of van Rossum differed significantly between different concentration intervals of L-636,499. At 10(-6) to 3 X 10(-6) mol l-1 the PA2-value was 5.99, whereas at 10(-5) to 3 X 10(-5) mol l-1 it was 5.59. Using PGF2 alpha as the agonist the PA2-value at the L-636,499 concentration interval 10(-5) to 3 X 10(-5) mol l-1 was 5.69. It may be concluded that the feline BA contains two receptor sites mediating prostanoid-induced contraction, one of which may be characterized as a thromboxane-sensitive (TP) receptor. L-636,499 can interact with both receptor sites with highest affinity for the TP receptor site.