Nitric oxide, a cellular messenger

SUBURO AM

Comunicaciones Biológicas (Buenos Aires)

Comunicaciones Biológicas

Lugar: Buenos Aires; Año: 1992 vol. 10 p. 91 - 114

0326-1956

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:72.0pt 90.0pt 72.0pt 90.0pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Nitric oxide (NO) is a free radical (.N = 0) that has been recently recognized as a messenger molecule in several tissues, including blood vessels, immune effector cells, peripheral nerves and the brain. This molecule is a short-lived intermediate in a biochemical pathway where L-arginine (L-Arg) is converted to L/citrulline and nitrite/nitrate. Being a nonpolar gas like 02 and CO2, NO behaves as a "diffusible intercellular messenger molecule" that does not require special membrane transporters. A short half-life due to chemical instability, plus enhanced breakdo"m by oxygen and oxygen-derived radicals, make unnecessary to have special enzymatic mechanisms for terminating NO action. In 1986, Furchgott and Ignarro independently proposed that NO was the endothelial-derived relaxing factor (EDRF), a mediator in the relaxation of vascular smooth muscle induced by a large number of agents, such as acety!choline and bradykinin. This hypothesis took into account the following properties shared by NO and EDRF: (a) they are labile substances that stimulate guanylate cyclase, with the resulting increase in cyclic guanosine monophosphate (cGMP) activating muscle relaxation; (b) they are rapidly inactivated by haemoglobin but not by methaemoglobin; (c) are inhibited by superoxide anions (02-), and potentiated by superoxide dismutase (SOD). It was later shown that stimulated endothelial cells synthesize NO in amounts enough to account for the biological effects of EDRF, namely, regulation of physiological vascular tone, blood pressure and tissue perfusion. Effects of NO depend on the available amount within the tissues. A low NO output mainly results in signal transduction and cGMP-mediated functional linkage between cells. By contrast, a large NO output, as in activated macrophages (100 nmol/hour per mg protein), is cytotoxic. These opposite roles reflect the existence of at least two different NO synthases. One enzyme is constitutively found in the vascular endothelium and nerve cells, where it generates low NO concentrations that activate the soluble guanylate cyclase. A different NO synthase, induced in activated macrophages and other cell types after appropriate stimulation, originates a prolonged NO synthesis.