Role of nitric oxide (NO) in hypothalamic function

Journal/Book: Z Rheumatol 1999; 58: 298-299. 1999;

Abstract: W Riedel; Max-Planck-Institut für physiologische und klinische Forschung W.G. Kerckhoff-Institut Bad Nauheim In the course of a complex redox reaction the gaseous radical nitric oxide (NO) is catalysed by conversion of L-arginine to L-citrulline by several subtypes of nitric oxide synthase (NOS). Presently known are one cytokine inducible form (iNOS) which becomes active only within hours after the inducing event and two constitutively expressed forms endothelial (eNOS) and neuronal (nNOS) which are regulated by the cytosolic concentration of free Ca2+. Brain nNOS is physiologically present in discrete populations of neurons. Hence NO should act quite selectively as a diffusible intercellular messenger though independent of the directional confinements existing for synaptically released transmitters. The modes of action of NO as a modulator of neuronal activity reflect its chemically dual character: similar to other transmitters/modulators using cGMP as their intracellular messenger NO acts as a messenger by activating the soluble guanylyl cyclase. Alternatively NO as a nitrosylating agent may enhance disulfide bonding of vicinal sulfhydryl (thiol) groups of the redox modulatory site of the NMDA receptor complex and thereby downregulate its Ca2+ channel activity. With each mode of action the responses to NO are ambiguous. Depending on the type of cGMP-controlled ion channels NO may excite or inhibit neurons. The action of NO on the NMDA receptor channel complex critically depends therefore on the redox state of its environment. The mammalian hypothalamus plays an important role in the control of autonomic and endocrine processes such as cardiovascular activity and secretion of stress hormones. Histochemical studies have revealed the presence of a large number of NOS containing neurons in the magnocellular and parvocellular subdivisions of hypothalamic nuclei. ... le

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