Distribution of free methylarginines in rat tissues and in the bovine brain

A sensitive and specific method for determining three forms of methylarginine, i.e., NG-monomethylarginine, NG,NG-dimethylarginine, and NG,N'G-dimethylarginine, in mammalian tissues was developed. After partial purification by ion-exchange chromatography, the methylarginines were derivatized to phenylthiocarbamyl compounds and quantitatively determined using HPLC with a reverse-phase C18 column. In rat organs, the highest concentrations of methylarginines were observed in the spleen. In rat brain, cerebellum and olfactory bulb contained large amounts of NG-monomethylarginine and NG,NG-dimethylarginine. A detailed study of the distribution of methylarginines in the bovine brain was also made, and the concentration of NG,N'G-dimethylarginine was almost the same in all regions. The cerebellar gray matter, hippocampus, and hypothalamus contained large amounts of methylarginines. The distribution of methylarginines seems to parallel the distribution of nitric oxide synthase, which is known to be inhibited by NG-monomethylarginine. This may indicate that methylarginines play some role in controlling nitric oxide synthase activity.