Cellular Signal Transduction and Nitric Oxide

Abstract

Nitric oxide (NO·) is an important regulatory determinant of vascular tissue homeostasis that evokes its functional effects through a broad range of signaling elements, including the phospholipase C/calcium signaling systems, tyrosine kinase signaling pathways, G-proteinlinked receptors, ion channels, cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP)-dependent pathways, and the apoptotic pathway. Traditionally, nitric oxide was thought to signal exclusively via its stimulation of guanylyl cyclase, inducing an increase in intracellular cGMP levels and, in turn, the allosteric activation of cGMPdependent kinase (protein kinase G [PKG]). However, more recent work has revealed that some of NO·’s signaling effects can also be transduced by S-nitros(yl)ation and tyrosine nitrosation. Moreover, in addition to the activation of PKG, the cGMP-dependent effects can also be mediated by other proteins whose activities are allosterically modified by cGMP (e.g., phosphodiesterases and ion channels), and via cross-activation of cAMP-dependent kinase (protein kinase A [PKA]). This chapter will cover NO·’s specific effects on signaling pathways in vascular smooth muscle cells, cardiomyocytes, endothelial cells, and platelets.