RT Journal Article
SR Electronic
T1 Effect of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of cyclic GMP phosphodiesterase, on human platelet aggregation.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 467
OP 471
VO 228
IS 2
A1 M Hagiwara
A1 T Endo
A1 T Kanayama
A1 H Hidaka
YR 1984
UL http://jpet.aspetjournals.org/content/228/2/467.abstract
AB The effects of a novel compound, 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), on cyclic nucleotide metabolism and in vitro aggregation of human platelets were investigated. The concentrations of MY-5445 producing 50% inhibition of human platelet aggregation induced by 3 microM ADP, 3 micrograms/ml of collagen and 100 micrograms/ml of arachidonic acid were 0.07, 0.02 and 0.17 microM, respectively. Addition of MY-5445 significantly elevated cyclic GMP content in human platelets but had no effect on cyclic AMP content, suggesting that the drug affects principally the cyclic GMP metabolism in the platelet. Although MY-5445 had no effect on either adenylate cyclase or guanylate cyclase activity, it inhibited specifically human platelet cyclic GMP phosphodiesterase which was separated from cyclic AMP phosphodiesterase by diethylaminoethyl-cellulose column chromatography. The inhibitory effect of MY-5445 on cyclic GMP phosphodiesterase was also demonstrated by direct binding of the enzyme to MY-5445 coupled Sepharose, which was a useful tool for purifying the cyclic GMP phosphodiesterase from human platelet. These results would suggest that MY-5445 inhibits human platelet aggregation by increasing cyclic GMP content and that it provides a useful probe for elucidating the role of cyclic GMP in platelet aggregation.