The mechanism for the inhibitory action of N-(3',4'-dimethoxycinnamoyl)anthranilic acid (tranilast) on the release reaction in platelets.
The molecular basis for the inhibitory action of the antiatopic drug, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), on the thrombin-induced release of a lysosomal enzyme, beta-N-acetylglucosaminidase, from washed rabbit platelets was investigated. Tranilast dose dependently increased cyclic AMP and cyclic GMP levels in thrombin-stimulated platelets, parallel with the inhibition of beta-N-acetylglucosaminidase release. There was no significant effect of Tranilast on adenylate or guanylate cyclase activity. Tranilast inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterases in a cell-free system. The data suggest that the inhibitory action of Tranilast on the release reaction in platelets was due at least in part to inhibition of cyclic nucleotide phosphodiesterases followed by an elevation of cyclic AMP and cyclic GMP levels.
Iwasa
Y
Y
Third Department of Internal Medicine, University of Yamanashi Medical School, Yamanashi-ken, Japan.
Iwasa
T
T
Yoshimura
T
T
Matsui
K
K
Onaya
T
T
D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000634:Aminoquinolines; D002614:Chelating Agents; D062367:ortho-Aminobenzoates; C035738:Quin2-acetoxymethyl ester; D000242:Cyclic AMP; D011493:Protein Kinase C; D000118:Acetylglucosaminidase; D006152:Cyclic GMP; C012293:tranilast; D002118:Calcium