CHARACTERIZATION OF THROMBOXANE A(2) PROSTAGLANDIN ENDOPEROXIDE RECEPTORS IN AORTA/

Thromboxane A(2)/prostaglandin endoperoxide receptor antagonists were studied in rat and guinea-pig aortas contracted with U-46619 (9,11-did eoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F-2 alpha) or 8-epi-pr ostaglandin F-2 alpha. In rat aorta, the antagonists competitively inh ibited contractions evoked by either agonist with a rank order of pote ncy as follows: BMS-180291 ([1s-(eso, xabicyclo[2.2.1]hept-2-yl]methyl ]-benzenepropanoic acid) greater than or equal to SQ 29,548 ([1s-[1 al pha,2 beta-(5z),3 beta,4 ]methyl-7-oxobicyclo-[2.2.1]hept-2-yl]-5-hept anoic acid) > daltroban (4-[2-(4-chlorobenzenesulfonylamino) ethyl]-be nzene acetic acid) greater than or equal to SQ 30,741 ([1s-[1 beta,2 a lpha(5z),3 alpha,4 o]methyl]-7-oxabicyclo[2.2.1]hept-2-yl-5-heptanoic acid) = AA-2414 -dioxo-zeta-phenyl-1,1,4-cyclohexadien-1-heptanoic aci d). In guinea-pig aorta, the antagonists competitively antagonized con tractions elicited by either agonist with the following rank order of potency: SQ 29,548 = AA-2414 greater than or equal to SQ 30,741 > dalt roban. Antagonism by BMS-180291 in guinea-pig aorta was not strictly c ompetitive. These findings indicate that thromboxane A(2)/prostaglandi n endoperoxide receptors in rat aortas are different from those in gui nea pigs. Because the actions of both agonists were equivalently antag onized by each of the antagonists in both rat and guinea-pig aortas, t he results do not support the hypothesis that U-46619 and 8-epi-prosta glandin F2 alpha elicit contractions via different receptor subtypes i n the aorta.