In recent years nitric oxide (NO) has emerged as a unique biological m
essenger. NO is a highly diffusible gas, synthesized from L-arginine b
y the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS
have been described, each with a specific distribution profile in the
brain and periphery. NOS subtype I is present, among other areas, in
the hippocampus, hypothalamus, pituitary and adrenal gland. Together t
hese structures form the limbic-hypothalamic-pituitary-adrenal (LHPA)
or stress axis, activation of which is one of the defining features of
a stress response. Evidence suggests that NO may modulate the release
of the stress hormones ACTH and corticosterone, and NOS activity and
transcription is increased in the LHPA axis following various stressfu
l stimuli. Furthermore, following activation of the stress axis, gluco
corticoids are thought to down-regulate the transcription and activity
of NOS via a feedback mechanism. Taken together, current data indicat
e a role for NO in the regulation of the LHPA axis, although at presen
t this role is not well defined. It has been suggested that NO may act
as a cellular communicator in plasticity and development, to facilita
te the activation or the release of other neurotransmitters, to mediat
e immune responses, and/or as a vasodilator in the regulation of blood
flow. In the following review we summarize some of the latest insight
s into the function of NO, with special attention to its relationship
with the LHPA axis.