EFFECT OF 5-HEXYNE-1,4-DIAMINE ON BRAIN J-AMINOBUTYRIC ACID METABOLISM IN RATS AND MICE

1. 5-Hexyne-1,4-diamine (RMI 71696) an enzyme-activated irreversible inhibitor of ornithine decarboxylase (EC 4.1.1.17), induces a rapid, long-lasting, dose-dependent decrease of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19) activity and, to a lesser extent, of glutamate decarboxylase (EC 4.1.1.15) in the brains of rats when injected intraperitoneally. The 4-aminobutyric acid concentration in whole brain increases five-fold over control values. 2. Pretreatment with pargyline, a potent inhibitor of monoamine oxidase (EC 1.4.3.4) abolishes the effects on 4-aminobutyric acid metabolism and potentiates the inhibitory effect of 5-hexyne-1.4-diamine on prostatic ornithine decarboxylase activity. 3. 5-hexyne-1.4-diamine is a substrate of monoamine oxidase but not of diamine oxidase (EC 1.4.3.6) and is oxidized by a mitochondrial suspension to 4-aminohex-5-ynoic acid. This is a known potent inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase and of glutamate decarboxylase. 4. 4-aminohex-5-ynoic acid is formed in vivo from 5-hexyne-1.4-diamine by the same mechanism. © 1979.