M-NINEsulphoximine is the toxic principle isolated from flour treated by the nitrogen trichloride, or 'Agne'. process (BENTLEY er al., MELUNBY, 1946 MELUNBY, , 1947 MWM and REINER, 1950). It is a potent convukant for all mammalian species testad, producing a semi-chronic seizure state within 12 to 24 hours after oral or puenteml administration (REINER et ai., 1950; TOWER, 1958~). It has also been shown to inhibit the growth of various microorganisms and to be counteracted in this respect by addition of methionine or glutamine to the culture media (HEATHCOTE and PACE, 1950; NEWEU and CARMAN, 1950). Inhibition of cerebral glutamine synthesis by methionine sulphoximine (PACE and MCDERMOTT, 1952) appears to be closely analogous to similar inhibition by methionhe sulphoxide in a variety of tissue preparations (BOREK et al., 1W; ELLIOTT and GALE, 1948; SPECK, 1949). The seizures ~induccd by methionine sulphoximine can be prevented or arrested by in vim sdministration of large doses of methionine, glutamine, or asparagine (RErNeR et a/., 1950; TOWER, 19596). Cerebral cortex slices from cats with such seizures exhibit during incubation in uirro a failure of 'bound' acetylcholine production, which can be corrected by in oitro addition of methionine, glutamine, or asparagine (TOWER, 19596; TOWER and ELLIOIT, 1953). These various observations suggest that methionine sulphoximine acts both as a methionine antagonist or antimetabolite and as an inhibitor of glutamine metabolism. It is not apparent whether or not the two effects ICC directly interrelated, nor is the exact mode of action of methionine sulphoximine ckp1. The studies reported here on metabolism of glutamic acid and glutamine in incubated slices of cat cerebral cortex were undertaken to obtain further information on thcsc points, since disturbances of glutamic acid metabolism appear to be common to many different seizure states (TOWFR, 19596). Some preliminary accounts have beca previously reported (TOWER, 19576; 19596). MATERIALS A N D METHODS AU studies wcrc carried out on stock, adult cats. DL-methionine sulphoximine was generously supplpd by the late Dr. L. REINITI of Wallaa and Tiernan Co.. Inc., Bclleville. New Jersey. Reagent grdc L -~~~I K I acid8obtaincd from Nutritiwal Biochemicals Corp., Ckveland, Ohio, and a&&mhu? Iripbo6phatc sodium (ATP) from S i p Chemical Co., St. Louis, Missouri. Analytically prre 2p)1Tdidiaonc and pyridoxal phosphate w e r~ kindly donated by Dr. L. S m of Mercksbsrpc and Dohmc Rcsarch Lsboraton'es, Rabway. New Jersey. All other chemicals were of w t p i c . obtaiad from usual commercial sources. ycre i n d d in cats by htrapcritoncal injection of 0.1 m-moles (IS-U)mg/kg body mya,dmahionint sulphoximine diaolvcd in 2 ml of0.9% NaCl solution. With this dose seizures 80
