TY - JOUR
T1 - A pyrrolidine-based specific inhibitor of cytosolic phospholipase A2α blocks arachidonic acid release in a variety of mammalian cells
AU - Ghomashchi, Farideh
AU - Stewart, Allison
AU - Hefner, Ying
AU - Ramanadham, Sasanka
AU - Turk, John
AU - Leslie, Christina C.
AU - Gelb, Michael H.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants HL50040 (M.H.G.), HL34304 and HL61378 (C.C.L.), and a Career Development Award from the American Diabetes Association (S.R.).
PY - 2001/8/6
Y1 - 2001/8/6
N2 - 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 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.
AB - 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 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.
KW - Arachidonic acid
KW - Cystolic phospholipase
KW - Pyrrolidine-based inhibitor
UR - http://www.scopus.com/inward/record.url?scp=0035817264&partnerID=8YFLogxK
U2 - 10.1016/S0005-2736(01)00349-2
DO - 10.1016/S0005-2736(01)00349-2
M3 - Article
C2 - 11470087
AN - SCOPUS:0035817264
SN - 0005-2736
VL - 1513
SP - 160
EP - 166
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 2
ER -