Nitric Oxide at the cross-road of immunoneuroendocrine interactions

RETTORI, V.; FERNÁNDEZ-SOLARI, J.; MOHN, C.E.; ZORRILLA ZUBILETE, M; PRESTIFILIPPO, J.P.; DE LA CAL, C.; DE LAURENTIIS, A.

Annals of the New York Academy of Sciences

Año: 2008

Nitric Oxide (NO) was initially described as a mediator of endothelial relaxation, now its participation is recognized in numerous physiological and pathological processes. It was demonstrated that LPS-stimulated CRH release involves NO production. Furthermore, it has been shown that IL-1, TNF-a, IL-6 and IL-2 can stimulate ACTH release from anterior pituitary via NO. Also, we found that NO released from hypothalamic NOergic neurons in response to NE diffuses to LHRH neurons where activates COX and GC with the consequent increase of PGE2 and cGMP, respectively, that lead to the exocytosis of LHRH granules. During pathological conditions, such as manganese intoxication, NO production is increased leading to increase in LHRH secretion that can advance puberty. In another study we demonstrated that NO reduces oxytocin, as well as vasopressin secretion from the posterior pituitary suggesting its modulatory role during dehydration. There was found an increase in NOS activity and protein in hippocampus and cerebellum in offspring of rats that were submitted to prenatal stress that correlated with behavioral changes in adults. Also NO participates in signal transduction pathways in peripheral tissue in physiological conditions such as in corticosterone release from the adrenal gland. Pathological conditions, such as tumors of head and neck that are treated with radiation are followed by xerostomy. In a rat model, radiation diminished NOS activity in the submandibulary gland followed by inhibition in salivary secretion.  In summary, this review describes the wide participation of NO in the cross-talk between neuroendocrine and neuroimmune systems in physiological and pathological processes.