p-Aminobenzoic acid, but not its metabolite p-acetamidobenzoic acid, inhibits thrombin induced thromboxane formation in human platelets in a non NSAID like manner.
We have previously shown that p-aminobenzoic acid (PABA) is acetylated by several cell lines and most peripheral blood cells, including platelets, to p-acetamidobenzoic acid (PACBA). The structural similarity of PABA and PACBA to local anesthetics and some non steroidal anti inflammatory drugs urged us to perform the present investigation. When human platelets were stimulated with thrombin to liberate AA, we found that PABA inhibited the production of thromboxane (TxB2) as measured with enzyme-linked immunosorbent assay. The inhibition was reversible and observed at PABA concentrations ranging between 55 and 1000 microM. At 328 microM PABA the production of TxB2 diminished by 87% (p = 0.013). PACBA in the same doses did not affect the production of TxB2. When platelets were incubated with [1-14C]AA, in the presence of PABA, the production of [1-14C]TxB2 was only slightly inhibited, according to analysis by high pressure liquid chromatography. Obviously PABA is not mainly acting as a prostaglandin H (cyclooxygenase) or Tx synthase inhibitor. It is rather affecting a step prior to thromboxane production, most likely the liberation of the precursor AA. In conclusion, our results demonstrate for the first time that PABA, a substance occurring in nature, inhibits endogenous TxB2 synthesis in human platelets and might thus exert profound effects on platelet AA metabolism.
Barbieri
B
B
Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge University Hospital, Sweden.
Papadogiannakis
N
N
Eneroth
P
P
Söderstedt
A
A
Stain-Malmgren
R
R
Olding
L B
LB
D010129:4-Aminobenzoic Acid / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000107:Acetylation; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D001693:Biological Transport, Active; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000097:blood; D062366:para-Aminobenzoates
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D062366:para-Aminobenzoates; C023730:Acedoben; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013917:Thrombin; D010129:4-Aminobenzoic Acid