Nitric Oxide and the Central Nervous System

During the last ten years, several investigators have reported that biological effects of endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) are actually activities of a signal molecule, nitric oxide (NO; Moncada el al., 1988). This molecule is synthesised by endothelial vascular cells (Palmer el al., 1987, 1988; Ignarro, 1990). Endogenous NO is involved in many biological processes. The horseshoe crab (Lilllulus polypherus), that exists for 500 million years, synthesises NO from L-arginine to avoid aggregation of its circulating haemocytes (Radomski el al., 1991), wltile the blood sucking insect Rhodnius prolixus uses NO in its prey for vasodilatation and platelet anti-aggregation (Ribeiro el al., 1993). The goldfish Carassius auralus (Bruning el al., 1995) and the frog Xenopus laevis (Bruning and Mayer, 1996) use NO as a molecule for neuronal signalling. Evidence has accumulated that endogenous NO regulates not only mammalian blood vessels but many other systems (Moncada and Higgs, 1991). Almost every mammalian cell/system is under influence of NO, involving endotheliumMdependent relaxation (Furchgott and Zawadzki, 1980), neurotransmission (Garthwaite el al., 1988; Gillespie el al., 1989) and cell-mediated ilmllune response (Nathan and Hibbs, 1991). Appropriately, NO was proclaimed as a Molecule ojlhe Year for 1992 by the journal Science (Koshland, 1992). In addition, the beneficial effects of glyceryl trinitrate in coronary heart disease, known since 1867, have been recently explained through NO (Anggard, 1994). Alfred Nobel, who invented nitroglycerine. used the drug himself to relieve his coronary heart problems (Snyder and Bredt, 1992; HOlscher el al., 1995). Recently, it has been found that NO can exert not only cytoprotective but also cytotoxic effects in mammalian cells (Snyder and Bredt, 1992; Krencke el al., 1997). Moreover, it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine with therapeutic opportunities (Snyder, 1993; Schmidt and \\Valter, 1994; Vallance and Moncada, 1994). Thus, the main goal of this thesis is to highlight the importance of this molecule, particularly in the neuropharmacology.