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 B2 production in human platelets. In this report we show that PABA and its acetylated metabolite p-acetamidobenzoic acid (PACBA) inhibit platelet aggregation induced by agonists 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 significantly inhibiting collagen aggregation, PABA and PACBA reduced the concomitant adenosine triphosphate (ATP) secretion by approximately 30 and 20%, respectively. The antiaggregatory effect does not seem to be mediated through cyclic adenosine monophosphate (cAMP) increase because in our experiments PABA and PACBA did not significantly affect cAMP levels. However, we have found that PABA and PACBA inhibit the intracellular aequorin indicated Ca2+ transient upon arachidonic acid stimulation. Our results describe a hitherto unknown effect of PABA and PACBA on platelet aggregation.
Barbieri
B
B
Vitamex/Numico, Norrköping, Sweden. Bruno.Barbieri@Vitamex.se
Stain-Malmgren
R
R
Papadogiannakis
N
N
D010129:4-Aminobenzoic Acid / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D062366:para-Aminobenzoates
D010975:Platelet Aggregation Inhibitors; D062366:para-Aminobenzoates; C023730:Acedoben; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D002118:Calcium; D010129:4-Aminobenzoic Acid