First Messengers

Publisher Summary First messengers are natural extracellular ligands that bind and activate receptors, which are subdivided as hormones, neurotransmitters, cytokines, lymphokines, growth factors, chemoattractants, etc. Each of these terms attempts to define a class of agents that take effect in a particular setting. Hormones are commonly released in small amounts at sites remote from the organs they target. On entering the circulation, they are diluted enormously and are subject to enzymes that break them down. Many of them circulate as complexes with specific binding proteins, reducing their free concentration still further. The result of all this is that their level in the vicinity of a target cell is likely to be extremely low and accordingly, the cell receptors must possess high affinity. Also, unlike hormones, the effects of growth factors are short range, generally influencing the growth and function of neighboring cells. Neurotransmitters are also first messengers, but their release and detection at chemical synapses contrast strongly with that of endocrine signals. This chapter highlights the fact that in addition to the transcriptional actions of hydrophobic messengers, there is increasing evidence for non-transcriptional effects, which take place rapidly and involve interactions with cell surface receptors. They include cAMP, Ca2+, diacylglycerol, and the 3-phosphorylated inositol lipids. The binding of ligands, measurement of their binding affinity, and heterogeneity of binding have also been discussed later in this chapter.