ABSTRACT
As a naturally occurring signaling molecule, nitric oxide is known to be an ac tive component of the inflammatory response, neurotransmission, and vasodila tation. To study each of these phenomena, investigators have adopted certain mode-systems in which to examine the genesis and cellular effects of NO. Thus, macrophages (anti-inflammatory effects), cardiac myocytes (contractile events), endothelial cells (vasoconstriction), and neurons (anoxic cell death) have pro vided the experimental settings for many of the NO-related studies published to date. Of present interest is the finding that in each of these systems, protein ki nase C (PKC) has been implicated in either the regulation of NO synthase (NOS) activity or its expression. Although other protein kinases have been associated with the regulation of NOS, much more information about PKC is available with regard to its regulation, subcellular localization of its related isoforms, experi mental methods for studying its cellular activity, and its role as a component of signaling pathways that govern the expression of NOS. This chapter first reviews aspects of the PKC literature that focus on the function and regulation of this enzyme in a cellular context with emphasis on the existence and functional speci ficity of its related isoforms. Following this general overview, discussion ad dresses the complex interplay among PKC, NOS, and NO. A model summariz ing the reciprocal interactions occurring between PKC and NOS is presented. It is proposed that while PKC is instrumental in directing the expression of NOS, the product NO may itself be involved in the regulation of PKC, as reflected by the sensitivity of PKC to NO and other cellular oxidants.
