Signal Transduction through cAMP and cGMP

Cells respond to hormones, neurotransmitters and other agents in two opposing ways. These are referred to as amplification (enhancement) and adaptation (diminution) (1). Amplification enables an organism or cell to respond to a very faint signal such as a low blood hormone concentration. Adaptation prevents constant background stimulation, or excessive stimulation, of a pathway. The cAMP cascade system illustrates two different kinds of amplification: the first is magnitude amplification, which is an increase in output molecules in greater numbers than input molecules; and the second is sensitivity amplification, which is a greater percentage increase in ouput than the percentage increase in input. An example of magnitude amplification would be the production of 100 cAMP molecules from 1 active molecule of adenylate cyclase, and sensitivity amplification could be an increase in cAMP-dependent protein kinase activity of 200% by 100% increase in cAMP. Both kinds of amplification can occur at each step of a cascade, although the overall magnification in a cascade can also be calculated. For example, the overall magnitude amplification for glucagon stimulation of glycogen breakdown in the liver is represented by the number of glucose molecules produced divided by the number of glucagon molecules added, and can be greater than 10,000.