A pyrrolidine-based specific inhibitor of cytosolic phospholipase A2α blocks arachidonic acid release in a variety of mammalian cells

We analyzed a recently reported (K. Seno, T. Okuno. K. Nishi. Y. Murakami, F. Watanabe., T. Matsuur, M. Wada, Y. Fujii, M. Yamada. T. Ogawa. T. Okada. H, Hashizume, M. Kii, S.-H. Hara, S. Hagishita, S. Nakamoto, J. Med. Chem. 43 (2000)) pyrrolidine-based inhibitor, pyrrolidine-1, against the human group IV cytosolic phospholipase A(2) alpha -isoform (cPLA(2)alpha). Pyrrolidine-1 inhibits cPLA(2)alpha by 50% when present at approx. 0.002 mole fraction in the interface in a number of in vitro assays. It is much less potent on the cPLA(2)gamma isoform, calcium-independent group VI PLA, and groups IIA, X, and V secreted PLA(2)s, Pyrrolidine-1 blocked all of the arachidonic acid released in Ca2+ ionophore-stimulated CHO cells stably transfected with cPLA(2 alpha), in zymosan- and okadaic acid-stimulated mouse peritoneal macrophages, and in ATP- and Ca2+ ionophore-stimulated MDCK cells. (C) 2001 Elsevier Science B.V. All rights reserved.