Often biochemical communication is triggered by certain substances after the actions of neurotransmitter at their respective receptors. These substances are called second messengers and the intracellular effects they cause may be responsible for long-term changes in the nervous system. They convey the message of the first messenger (which is the neurotransmitter) from the cell membrane to the cell’s internal biochemical machinery. The effects elicited by these second messengers may endure a few milliseconds to as long as several minutes. Three types of second messengers can be discerned:

Hydrophobic molecules: water-insoluble molecules, often associated with the cellular membrane.
Hydrophilic molecules: water-soluble molecules, like cAMP, that are located within the cytosol, or intracellular fluid.
Gases: can diffuse through both cellular membranes and cytosol.

An Example of a System

The initial step in this example of the activation of a second messengers involves ATP (adenosine triphosphate), the chemical source of cellular energy, a molecule that is present throughout the cell. So, in this example, the neurotransmitter norepinephrine binds to its receptors on the surface of the neurons. The activated receptors binds a protein called G protein on the inside of the membrane. This activated G proteins subsequently causes the enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (or cAMP). This second messenger, cAMP, exerts a variety of influences on the cell, ranging from changes in the function of the ion channels in the membrane to changes in the expression of the genes in the nucleus.

cAMP is called a second messenger because it acts as after the first messenger, the transmitter chemical, has crossed the synaptic space and attached itself to a receptor.

It has been shown that a deregulation of the cAMP pathways can potentially lead to an aberrant activation of cAMP-controlled genes in the cell nucleus, which in turn could lead to the development of cancer. Furthermore, it has been suggested by research that cAMP affects the function of the prefrontal cortex, which is responsible for higher-order thinking, through regulation of the relevant ion channels.

Further Roles

Second messengers are also thought to play a role in the manufacturing and release of neurotransmitters, intracellular movements, carbohydrate mechanism in the cerebrum (the largest part of the brain, consisting out of two large hemispheres) and the processes of growth and development. The possible direct effects of these second messengers on the genetic material that can be found in cells may lead to long-term alterations of behavior.