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

AbstractWe 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 A2 α-isoform (cPLA2α). Pyrrolidine-1 inhibits cPLA2α 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 cPLA2γ isoform, calcium-independent group VI PLA2 and groups IIA, X, and V secreted PLA2s. Pyrrolidine-1 blocked all of the arachidonic acid released in Ca2+ ionophore-stimulated CHO cells stably transfected with cPLA2α, in zymosan- and okadaic acid-stimulated mouse peritoneal macrophages, and in ATP- and Ca2+ ionophore-stimulated MDCK cells