Cardiovascular Drug Reviews Vol. 25, No. 1, pp. 61–75 C  2007 The Authors Journal compilation C  2007 Blackwell Publishing Inc. N -(p-Amylcinnamoyl)anthranilic Acid (ACA): A Phospholipase A 2 Inhibitor and TRP Channel Blocker Christian Harteneck 1 , Henning Frenzel 1 , and Robert Kraft 2 1 Institut f ¨ ur Pharmakologie, Charit´ e – Universit¨ atsmedizin Berlin, Berlin, Germany 2 Carl-Ludwig-Institut f¨ ur Physiologie, Universit¨ at Leipzig, Leipzig, Germany Keywords: Anthranilic acid — Fenamate — Inflammation — Insulin se- cretion — Intracellular calcium — Phospholipase A 2 — TRP channels. ABSTRACT Phospholipase A 2 enzymes display a superfamily of structurally different enzymes classified in at least nine subfamilies by biochemical and structural properties. N -(p- amylcinnamoyl)anthranilic acid commonly referred to as ACA is often used as a broad- spectrum inhibitor for the characterization of phospholipase A 2 –mediated pathways. Com- pounds like ACA and ACA-like structures have been described to block the receptor-induced release of arachidonic acid and subsequent signaling cascades in the pancreas and the car- diovascular system. We showed that ACA directly blocks several transient receptor potential (TRP) channels (TRPC6, TRPM2, TRP and TRPM8). With respect to the published data of ACA in the phospholipase A 2 field, the finding that ACA blocks diacylglycerol-activated TRP channels is of specific interest as it offers the opportunity to interfere with receptor- induced calcium-dependent signaling processes in platelets and vascular smooth muscle cells. Overall, N -phenylcinnamides, as a new pharmaceutical lead structure, form the first class of synthetic TRP channel blockers and represent a promising start for the development of small organic TRP channel–specific blockers. Address correspondence and reprint requests to: Dr. Christian Harteneck. Institut f¨ ur Pharmakologie, Charit´ e Campus Benjamin Franklin, Thielallee 69-73, 14195 Berlin, Germany. Tel.: +49-30-84451825; Fax: +49-30- 84451818; E-mail: Christian.Harteneck@charite.de 61