Nitric oxide, interleukin and prostaglandin interactions affecting the magnocellular system

Abstract Magnocellular neurons are innervated by an excitatory histaminergic pathway. They also express neuronal NO synthase, interleukin-1β (IL-1β) and cyclo-oxygenase (COX). In normally hydrated rats when NO synthase activity is inhibited with N G -nitro- l -arginine methyl ester ( l -NAME), administered intracerebroventricularly (i.c.v.), OT concentration in plasma increases. In the present study, the increase in hormone after l -NAME is attenuated by indomethacin, an inhibitor of COX, as well as by antagonists of histamine receptors at H 1 (pyrilamine) and H 2 (cimetidine) subtypes injected i.c.v. Moreover, enhanced OT secretion induced by centrally administered IL-1β, but not naloxone (opiate receptor antagonist), is prevented by indomethacin. PGE 2 and PGD 2 (i.c.v.) stimulate OT release, but only PGD 2 affects circulating vasopressin levels. Thus, NO inhibits release of OT stimulated by: (1) a COX-dependent mechanism, i.e. NO→−(COX→+PG→+OT release); (2) histamine, i.e. NO→−(histamine→H 1 and H 2 receptors→+OT release); and possibly (3) IL-1β, i.e. NO→−(IL-1β→+COX→+PG→+OT release). These interactions of NO, cytokine and histamine may be important for management of stress-induced activation of neuroendocrine systems.