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 plat elets, to p-acetamidobenzoic acid (PACBA). The structural similarity o f PABA and PACBA to local anesthetics and some non steroidal anti infl ammatory drugs urged us to perform the present investigation. When hum an platelets were stimulated with thrombin to liberate AA, we found th at PABA inhibited the production of thromboxane (TxB(2)) as measured w ith enzyme-linked immunosorbent assay. The inhibition was reversible a nd observed at PABA concentrations ranging between 55 and 1000 mu M. A t 328 mu M PABA the production of TxB(2) diminished by 87% (p=0.013). PACBA in the same doses did not affect the production of TxB(2). When platelets were incubated with [1-C-14]AA, in the presence of PABA, the production of [1-C-14]TxB(2) was only slightly inhibited, according t o analysis by high pressure liquid chromatography. Obviously PABA is n ot mainly acting as a prostaglandin H (cyclooxygenase) or Tx synthase inhibitor. It is rather affecting a step prior to thromboxane producti on, most likely the liberation of the precursor AA. In conclusion, our results demonstrate for the first time that PABA, a substance occurri ng in nature, inhibits endogenous TxB(2) synthesis in human platelets and might thus exert profound effects on platelet AA metabolism. (C) 1 997 Elsevier Science Ltd.