6.6: Paracrine Signaling

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions.

Nitric oxide as a Paracrine Signaling Molecule

Blood vessels contain several layers of cells. The innermost layer of cells called the endothelium have nitric oxide synthase, which produces nitric oxide as a paracrine mediator. The nitric oxide that reaches the blood does not contribute to signaling but immediately reacts with biochemicals, such as hemoglobin. However, nitric oxide molecules that diffuse towards the smooth muscle cells surrounding the blood vessel facilitate their relaxation and vasodilation, and ultimately an decrease in blood pressure. At the molecular level, this signaling mechanism involves the binding of the nitric oxide molecules to guanylate cyclase receptors, which increases the levels of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells.

Paracrine Signaling and Blood Clotting

Another example of paracrine signaling is blood clotting. When a blood vessel is damaged and begins to bleed, the endothelium has been broken. Broken endothelial tissue releases von Willebrand factors (vWF), which bind to platelets cells circulating in the blood via paracrine signaling. Meanwhile, collagen fibers under the endothelial cells also bind to the platelets. Several other platelet proteins are subsequently activated and released by the platelets. These proteins then activate more platelets via paracrine signaling. A complex series of reactions between many clotting factors forms a substance known as fibrin, which holds the blood clot together and patches the broken endothelium.

Cells use paracrine signaling to communicate with their neighboring cells.

In paracrine signaling, a cell secretes signaling molecules that can diffuse over short distances.

As a result, such molecules can only trigger a response in cells with specific receptors in the immediate vicinity.

In fact, signaling molecules that are not bound to the receptors are quickly degraded by enzymes present in the extracellular matrix.

For example, physical activities like exercise increase the requirement for oxygen in skeletal muscle tissues. To fulfill this need for more oxygen, the endothelial cells lining the inner circumference of the blood vessels in this region secrete nitric oxide gas, or NO, as a paracrine mediator.

NO enters the extracellular matrix, and diffuses into the neighboring smooth muscle cells, causing them to relax.

As a result, the blood vessel dilates, increasing the blood flow to the deoxygenated tissues.

However, similar to other paracrine signaling molecules, NO degrades rapidly outside the endothelial cell and can only trigger a localized response.