Electroanalytical techniques for the in vivo measurement of neurotransmitters in brain tissue have been applied especially to the catecholamines, which are easily oxidizable. Measurements are, however, complicated by the presence of ascorbic acid (AA) in brain tissue. Lane et al. have been able to circumvent this problem, at least in part, by the application of differential pulse voltametry (DPV) to a surface-modified platinum electrode, obtaining distinct oxidation current peaks in recordings from the rat neostriatum which are attributed to AA and to dopamine (DA), respectively, but which are also unstable. We have recently described a new type of electrode, consisting of a pyrolytic carbon fibre 8 micrometers thick and 0.5 mm long. We now report that the DPV method used in conjunction with an electrochemical treatment of this electrode yields stable and reproducible peaks in which catecholamines and AA are resolved from each other. Moreover, pharmacological investigations suggest that the catecholamine peak measured in vivo in the rat neostriatum should be attributed to 3, 4-dihydroxyphenylacetic acid (DOPAC), suggesting that our technique may be a useful means of following dopaminergic activity in vivo.

An electrochemical microsystem using three electrodes is described. The active surface of the working electrode is a carbon fiber of 8-µ o.d. In normal pulse polarography, this

Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages fromTrypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence ofl-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows thatl-arginine availability modulates NO production. Trypanosomes use l-arginine for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover, arginase activity is up-regulated in macrophages from infected mice from the first days of infection. Arginase competes with NOS-II for their common substrate, l-arginine. In vitro, arginase inhibitors decreased urea production, increased macrophage nitrite production, and restored trypanosome killing. In vivo, a dramatic decrease inl-arginine concentration was observed in plasma from infected mice. In situ restoration of NO production and trypanosome killing were observed when excess l-arginine, but notd-arginine or l-arginine plusN ω-nitro-l-arginine (a NOS inhibitor), was injected into the peritoneum of infected mice. These data indicate the role of l-arginine depletion, induced by arginase and parasites, in modulating the l-arginine–NO pathway under pathophysiological conditions.

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