Chapter 13

Communication and Signaling in Medicinal Chemistry

Robert E. Smith

Abstract

To sustain life and good health, it is essential that cells and tissues can communicate with each other. Organelles within cells, cells within tissues, tissues within our body, and all of the bodies in a society must sense their internal and external environments and respond appropriately to changes. Hormones, neurotransmitters and cytokines can act as primary messengers. Secondary messengers include is Ca2+, IP3 and diacyl glycerol (produced by the hydrolysis of phosphoinositides), arachidonic acid (produced by the hydrolysis of phospholipids that have arachidonoyl on carbon number 2 of the glycerol backbone), ceramide, eicosanoids, lysophosphatidic acid, NO (nitric oxide), cAMP and cGMP. The IP3 receptor, or IP3R is a membrane-bound complex of glycoproteins. It is a Ca2+ channel that is activated by IP3, which is a secondary intracellular messenger. Inter- and intracellular communication can be thought of as a network that contains many items (nodes) that have anywhere from one to thousands of connections. The most widely connected nodes are called hubs. Probably the major genetic hub in human and many other mammalian cells is the gene TP53 which codes for the protein p53. About 50% of all human cancers have one or more mutations in p53 that alter DNA transcription.

Total Pages: 538-551 (14)

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