p-Aminobenzoic acid and its metabolite p-acetamidobenzoic acid inhibit agonist-induced aggregation and arachidonic acid-induced [Ca2+](i) transients in human platelets

We have previously found that the naturally occurring amine p-aminobenzoic acid (PABA) inhibits the thrombin-induced thromboxane B-2 production in hum an platelets. In this report we show that PABA and its acetylated metabolit e p-acetamidobenzoic acid (PACBA) inhibit platelet aggregation induced by a gonists such as adenosine diphosphate (ADP) and arachidonic acid (AA). Both substances were equipotent to acetylsalicylic acid regarding inhibition of ADP-induced aggregation and approximately 50% as potent as acetylsalicylic acid regarding arachidonic acid-induced aggregation. Although not signific antly inhibiting collagen aggregation, PABA and PACBA reduced the concomita nt adenosine triphosphate (ATP) secretion by approximately 30 and 20%, resp ectively. The antiaggregatory effect does not seem to be mediated through c yclic adenosine monophosphate (cAMP) increase because in our experiments PA BA and PACBA did not significantly affect cAMP levels. However, we have fou nd that PABA and PACBA inhibit the intracellular aequorin indicated Ca2+ tr ansient upon arachidonic acid stimulation. Our results describe a hitherto unknown effect of PABA and PACBA on platelet aggregation. (C) 1999 Elsevier Science Ltd. All rights reserved.