Nitric oxide signalling mechanisms

I. MECHANISMS OF NITRIC OXIDE SIGNALING IN VASCULAR CELLS... 

L.J. Ignarro, Nitric-Oxide - A novel signal transduction mechanism for transcellular communication. 

Three phases of receptor-mediated signaling can be identified 178 Four distinct molecular mechanisms that link agonist occupancy of cell-surface receptors to functional responses have been identified 178 Cross-talk can occur between intracellular signaling pathways 179 Signaling molecules can activate gene transcription 181 Nitric oxide acts as an intercellular signaling molecule in the central nervous system 181... 

The interaction of estrogen receptors with signaling systems of the cell membrane that respond to growth factors and mediate nongenomic, fast actions of estrogens will be reviewed as well. These mechanisms have a growing importance in the comprehension of phenomena like the induction of endothelial NOS (nitric oxide synthase) by estrogens (Rubanyi et al. 2002). 

Although NO does not itself use a G-protein for signalling, the mechanism of NO production in vascular endothelium is initiated by IP3 via a G-protein-linked acetylcholine receptor on the cell surface. The IP3 causes activation of nitric oxide synthase via calcium- calmodulin and the NO generated diffuses from the endothelial cell into the adjacent smooth muscle cell where cGMP is produced. 

Figure 25.3 Presentation of estradiol to A. endothelial cells affects signaling. (A) Physiological levels of estradiol (E2) complexed with albumin do not elicit the production of nitric oxide when presented to cultured endothelial cells although E2-albumin binds to caveolar SR-B1. (B) Physiological levels of estradiol complexed with HDL elicit the production of nitric oxide by activating AMPK and then eNOS. Although it is depicted in this figure that AMPK is activated by binding of estradiol to the estrogen receptor, B. this mechanism has not been experimentally demonstrated. Other mechanisms of E2-HDL activation of AMPK and eNOS are thus possible (See also color insert).

Ignarro, L. J. (1991). Signal transduction mechanisms involving nitric oxide. Biochem. Pharmacol. 41, 485-490. 

Ignarro, L. J. (1990b). Nitric oxide A novel signal transduction mechanism for transcel-lular communication. Hypertension (Dallas) 16, 477-483. 

VI. SIGNALING MECHANISM OF INTERLEUKIN 1-INDUCED EXPRESSION OF NITRIC OXIDE SYNTHASE... 

Corbett, J. A., Sweetland, M. A., Lancaster, J. R., Jr., and McDaniel, M. L. (1993a). A 1 hour pulse with IL-lb induces the formation of nitric oxide and inhibits insulin secretion by rat islets of Langerhans Evidence for a tyrosine kinase signaling mechanism. FASEBJ. 7, 369-374. 

The signal transduction mechanisms triggered by binding of ET-1 to its vascular receptors include stimulation of phospholipase C, formation of inositol trisphosphate, and release of calcium from the endoplasmic reticulum, which results in vasoconstriction. Conversely, stimulation of PGI2 and nitric oxide synthesis results in decreased intracellular calcium concentration and vasodilation. 

NITRIC OXIDE SYNTHESIS, SIGNALING MECHANISMS, INACTIVATION... 

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