TY - JOUR
AU - Robertson, A.D.
AB - 1 BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti‐aggregatory concentration‐effect curves to BW 245C were displaced in a parallel manner. The shifts accorded with a Schild plot slope of unity and a pKB of 9.26. 2 Inhibition of platelet aggregation by prostaglandin D2 (PGD2) was antagonized with a similar potency, as were the relaxation effects of BW 245C and PGD2 in the rabbit jugular vein. BW A868C can, therefore, be classified as a DP‐receptor antagonist. 3 Actions of BW A868C at other prostaglandin receptors (IP, EP1, EP2, TP and FP) were excluded at concentrations up to 1,000 times higher than the DP‐receptor affinity. 4 Analyses of BW 245C‐ and PGD2‐mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C. In rabbit jugular vein a resistant phase of agonism was detectable, indicating that both agonists exerted effects through another receptor (possibly EP2). Also, PGD2, in addition to its anti‐aggregatory effect on platelets, demonstrated a pro‐aggregatory action in the presence of BW A868C. 5 The contractile effects of PGD2 in guinea‐pig tracheal strips were resistant to 10 μm BW A868C indicating that they were not mediated through DP‐receptors. 6 To our knowledge this is the first account of a well‐classified competitive antagonist at the DP‐receptor. Its potency and selectivity make it an important new tool in prostanoid receptor classification and identification.
TI - The classification of prostaglandin DP‐receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist
JF - British Journal of Pharmacology
DO - 10.1111/j.1476-5381.1989.tb11816.x
DA - 1989-02-01
UR - https://www.deepdyve.com/lp/wiley/the-classification-of-prostaglandin-dp-receptors-in-platelets-and-Sft6nJmfWb
SP - 291
VL - 96
IS - 2
DP - DeepDyve
ER -