THE ACTIONS OF NO IN THE CENTRAL-NERVOUS-SYSTEM AND IN THYMOCYTES

Nitrogen monoxide (NO) has been suggested to be involved in many physi ological and pathological functions. In rat hippocampus, chemical NO d onors stimulated noradrenaline release in the presence of thiols such as dithiothreitol and L-cysteine. S-Nitrosocysteine, which is proposed to be a stable and endogenous S-nitrosothiol molecule, stimulated nor adrenaline release by itself. The effect of S-nitrosothiol on noradren aline release was calmodulin-dependent and cyclic GMP-independent. S-N itrosocysteine was incorporated into the slice via the L-type-like ami no acid transporter. These findings suggest the physiological signific ance of S-nitrosocysteine on neurotransmitter release and propose the existence of a specific uptake system of S-nitrosothiols in neuronal t issues. In rat thymocytes, chemical NO donors inhibited DNA synthesis. Hydrocortisone treatment in vivo inhibited DNA synthesis via the expr ession of the inducible NO synthase protein, and the accumulation of N O and cyclic GMP. Although it is known that glucocorticoids regulate i nducible NO synthase expression negatively in several types of cells i n vitro, glucocorticoid treatment in vivo regulates the expression pos itively. In primary cultured rat glial cells, a combination of cytokin es stimulated production of nitrite via expression of inducible NO syn thase. In these cells, simultaneous addition of endothelin decreased i nducible NO synthase expression induced by cytokines. On the other han d, pretreatment with endothelin for 24 hr enhanced the inducible NO sy nthase expression. Endothelin has two effects on inducible NO synthase expression, positive and negative, depending on treatment time. The a ctions of NO on the hippocampus and thymocytes and the regulation of i nducible NO synthase expression in glial cells are discussed.