Nitric oxide intercellular signaling

Nitric oxide (NO) is an intercellular signaling molecule that can inhibit neuronal energy production (Brorson et al., 1999 Malefic et al., 2004). It has been found that NO donors cause large increases in extracellular adenosine in cultures of forebrain neurons (Rosenberg et al., 2000). These were shown to be caused by NO release, and the accumulation of adenosine was not blocked by probenecid (ENT blocker) or GMP (a blocker of AMP hydrolysis), suggesting that adenosine was likely of intracellular origin. Indeed, it was found that NO donors caused a decrease in intracellular ATP and the inhibition of adenosine kinase activity, possibly due to the rise in adenosine. 

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... 

Stern JE. Nitric oxide and homeostatic control an intercellular signalling molecule contributing to autonomic and neuroendocrine integration Prog Biophys Mol Biol. 2004 84 197-215. 

Murad, F., Forstermann, U., Nakane, M., Pollock, J., Tracey, R., Matsumoto, T., and Buechler, W. (1993). The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication. Adv. Second Messenger Phosphoprotein Res. 28,101-109. 

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