Signal Specificity

Signal molecules bind with high affinity to their target receptors, forming a receptor-ligand complex. This means that the attraction between the signal molecule, or ligand, and the receptor is very strong and very specific. Once the receptor-ligand complex is formed, it tends to stay in place until one or more of the molecules is broken down.

When hormones, which are long-distance signaling molecules, are secreted into the bloodstream by endocrine cells, they have the potential to bind to receptors in every cell in the body. However, because hormones only have high affinity to their specific receptors, the hormones are able to target only the cells that present those receptors. In addition, because hormones need time to reach target cells that can be very far away from the signaling cells, they must stay intact in the bloodstream long enough for them to reach their targets. Thus, hormones are degraded very slowly once they are released into the bloodstream. Finally, the concentration of any given hormone in the blood is necessarily diluted because the hormones spread out by diffusion after they are secreted. Hormones are effective at low concentrations, usually less than 10^–8 M (mole), which is the molarity of a solution, or the number of moles of a solute dissolved in 1 liter of solution.

Compared to hormones, neurotransmitters, which are the means of the transmission of signals by nerve cells at a synapse, act swiftly on their target cells. The electrical signals that tell a neuron to release neurotransmitters are very quick. Once released, the neurotransmitters only have to diffuse across 20 to 40 nanometers of extracellular space to reach their targets. Neurotransmitters work at high concentrations because they do not have time to diffuse into the body. The close proximity between the nerve terminus and the target cell, where the signal is received, also contributes to the specificity of neurotransmitter signal molecules. Since neurotransmitters do not have far to travel to reach their targets, the affinity of a neurotransmitter to its receptor does not need to be as great as the affinity between a hormone and its receptor. The neurotransmitter-receptor complex dissociates quickly, especially compared to a hormone-receptor complex. Free-floating neurotransmitters are also quickly removed from the extracellular space, either by enzymatic degradation, which is the breakdown of signal molecules through enzyme activity, by cellular uptake into the nerve or target cell, or by downregulation of receptors and a decrease in neurotransmitter release. Downregulation of receptors is the reduction in the number of such receptors in the plasma membrane. Neuronal signaling is a specific kind of short-distance, or paracrine, signaling, but it is representative of the mechanism by which all short-distance signals target specific receptors. Signal molecules in contact-dependent signaling and autocrine signaling also depend upon the close proximity of their receptors to bind to them specifically. The farther away from the signaling cell the signal molecule diffuses, the less likely it is to bind to its target cell. Short-distance signal molecules require high concentration and close proximity to the target to form receptor-ligand complexes.

Nitric oxide (NO) is a special case of short-distance signaling. NO is a small, inorganic molecule that acts as a signaling molecule in vertebrates, some invertebrates, and some bacteria. NO is produced in the cytoplasm by an enzyme called NO synthase, and because NO is so small, it readily diffuses out of the cell that produces it and into neighboring cells.

NO signals many different cellular responses, including the dilation of blood vessels, which is why nitroglycerin pills are used to treat patients with angina, a condition of severe chest pain and a symptom of heart disease. Nitroglycerin is metabolized to yield NO, which is very short-lived in the body. When NO is introduced to heart tissue, for example, NO causes an increase in the signaling molecule cyclic guanosine monophosphate (cGMP). An increase in cGMP creates a signaling pathway in which arteries in the heart react immediately to the presence of the NO. In the presence of NO, the smooth muscle in the arteries relaxes and the vessels expand. When combined with cGMP, the NO is quickly diffused. This reaction occurs rapidly, so the dilated arteries increase blood supply to the heart equally quickly, which is essential for reducing heart stress.