Demonstration of endogenous inhibitors of monoamine oxidase in dog cerebrospinal fluid

We investigated the existence of endogenous inhibitors of monoamine oxidase(MAO) in cerebrospinal fluid(CSF). Normal CSF in dog inhibited MAO in mouse, rat, dog and monkey brain mitochondria with 5-HT and β-PEA as substrates. This inhibitory activity was also present in rabbit, monkey and human CSF. Addition of CSF to dog brain mitochondrial MAO inhibited the deamination of 5-HT and β-PEA and the inhibition was increased with increasing amounts of CSF added. CSF was treated in various ways, such as heating it in a boiling water bath ( 90 ℃, 20 min) and digestion by incubation with crude pepsin, trypsin and chymotrypsin. Heat treatment exhibited no effect on the inhibition. Digestion with trypsin and chymotrypsin reduced the MAO inhibitory activity to 40 or 5 % of that originally present. After ultrafiltration of the CSF through Centrisalt I Sartorius membranes to remove substance ＞ 10,000 M.W. , significant inhibitory activity persisted. This suggested that MAO inhibitor in CSF is a protein or peptide of less than 10,000 M.W. These results demonstrate that CSF contains an endogenous substance that acts like MAO inhibitor drugs to inhibit type A and type B MAO.