Toshihiko Murayama and Yasuyuki Nomura
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido
University, Sapporo 060, Japan
Abstract: Nitrogen monoxide (NO) has been suggested to be involved
in many physiological and pathological functions. In rat hippocampus, chemical
NO donors 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 noradrenaline
release by itself. The effect of S-nitrosothiol on noradrenaline release
was calmodulin-dependent and cyclic GMP-independent. S-Nitrosocysteine was
incorporated into the slice via the L-type-like amino acid transporter.
These findings suggest the physiological significance of S-nitrosocysteine
on neurotransmitter release and propose the existence of a specific uptake
system of S-nitrosothiols in neuronal tissues. In rat thymocytes, chemical
NO donors inhibited DNA synthesis. Hydrocortisone treatment in vivo inhibited
DNA synthesis via the expression of the inducible NO synthase protein, and
the accumulation of NO and cyclic GMP. Although it is known that glucocorticoids
regulate inducible NO synthase expression negatively in several types of
cells in vitro, glucocorticoid treatment in vivo regulates the expression
positively. In primary cultured rat glial cells, a combination of cytokines
stimulated production of nitrite via expression of inducible NO synthase.
In these cells, simultaneous addition of endothelin decreased inducible
NO synthase expression induced by cytokines. On the other hand, pretreatment
with endothelin for 24 hr enhanced the inducible NO synthase expression.
Endothelin has two effects on inducible NO synthase expression, positive
and negative, depending on treatment time. The actions of NO on the hippocampus
and thymocytes and the regulation of inducible NO synthase expression in
glial cells are discussed.
Keywords: S-Nitrosocysteine, Amino acid transporter, Hippocampus, Thymocyte,
Glial cell