Prostacyclin is a tissue hormone that belongs to the series 2 prostaglandins. The hormone is produced mainly in vascular endothelial cells and smooth muscle cells from arachidonic acid. It has a local vasodilatory effect, increases pain by sensitizing nociceptors, induces fever, and greatly inhibits platelet aggregation.
What is prostacyclin?
Prostacyclin, also known as prostaglandin l2 or PGl2 for short, is considered to belong to the group of five tissue hormones in the series-2 prostaglandins. The hormone, which is found only in animal cells, but not in plant cells. The synthesis of prostaglandins is closely linked to lipid metabolism. Various fatty acids with 20 carbon atoms each are formed via the path of dehydration and elongation of the carbon chains. Arachidonic acid, one of the newly formed fatty acids, is quadruply unsaturated and the starting material for prostacyclin. The endogenous synthesis takes place mainly in endothelial cells of the vessels and in cells of the smooth muscles. The chemical molecular formula of procyclin is C20H32O5. It shows that the hormone is composed only of the three elements carbon, hydrogen and oxygen. With the exception of prostaglandin F2, in which 34 instead of 32 hydrogen atoms are bound, all five series 2 prostaglandins have the same chemical molecular formula. The sometimes very different enzymatic action is due to the slightly different tertiary structure of each compound.
Function, action, and roles
Series-2 prostaglandins act largely as antagonists of series-1 prostaglandins, which exhibit anti-inflammatory and anticoagulant activity. Series-2 prostaglandins, on the other hand, increase inflammatory responses, constrict blood vessels, and enhance blood clotting processes. In addition, they sensitize nociceptors so that pain sensations are perceived more strongly. One of the main functions of prostacyclin, which belongs to the series 2 prostaglandins, is, together with prostaglandin E2, to induce local inflammatory reactions in the body, e.g. in the case of injuries, and to provide increased pain sensation. The hormone docks onto so-called IP receptors, G-protein-coupled membrane receptors specialized for prostacyclin, and causes the cell to react in certain ways via the receptor. Vascular permeability is increased, resulting in tissue swelling. Redness visible from the outside is based on the increased blood flow to the tissue at the injured site that triggered the reactions. The increase in pain comes from increased sensitization of the nerve endings of the nociceptors. A very important role of procyclin, which is synthesized in all vascular endothelial cells, is to prevent vascular contraction. This occurs via the increased formation of cyclic adenosine monophosphate (cAMP), which is the antagonist of thromboxane formed in platelets. Via the effective inhibition of thromboxane, prostacyclin is considered the most potent endogenous platelet inhibitor. The hormone also inhibits the so-called MAP kinase pathway, which involves multistep signal transduction pathways. MAP kinase is involved in cell differentiation, embryogenesis, and apoptosis, or programmed cell death.
Formation, occurrence, properties, and optimal levels
Prostacyclin is nearly ubiquitous in almost all human tissues and is synthesized primarily in the endothelial cells, which form the innermost layer of the walls of blood and lymphatic vessels in a unicellular layer as squamous epithelium. The number of endothelial cells in humans is an unimaginable 10,000 billion, and the cells are in contact with the blood over a total area of 4,000 to 7,000 square meters. In the endothelial cells, the enzyme prostacyclin synthase catalyzes prostacyclin from arachidonic acid via the intermediate prostaglandin PGH2. Prostacyclin synthase is found in humans as a membrane protein in the endoplasmic reticulum of cells of nearly all tissue types. Arachidonic acid, the starting substance for prostacyclin, is found in many foods of animal origin. Its content is particularly high in lard, at 1,700 milligrams per 100 grams. With a half-life of only 3 minutes, the hormone is subject to rapid bio-catalytic-enzymatic conversions, and the concentration can rise sharply to 15 – 20 times the normal value within minutes, depending on the situation, e.g. during general anesthesia in operations.Therefore, the specification of an optimal concentration or the specification of reference values is not indicated.
Diseases and disorders
In lipid metabolism, various disorders of synthesis performance can occur. If the two essential omega-6 and omega-3 fatty acids are lacking in metabolism, series-1 and series-3 prostaglandins cannot be synthesized, but series-2 prostaglandins, including prostacyclin, can. Here, the two cyclooxygenases, COX-1 and COX-2 play an essential role. Both enzymes are expressed by different genes, and both enzymes have different tasks. The protein structures of COX-1 and COX-2 cyclooxygenases could not be sequenced until the 1990s. Also, it was not until the late 1990s that it was realized that the synthesis of prostaglandins could be controlled by the availability of COX-1 and COX-2. The two cyclooxygenases are globular proteins of about 600 amino acids whose bio-active centers are almost identical despite different physiological properties. If prostacyclin synthesis is too low, rather unspecific symptoms such as increased tendency to thrombosis and circulatory disorders occur. For example, the very rare and hereditary Hermansky-Pudlack syndrome is associated with pathologically decreased prostacyclin synthesis. The disease is characterized by ocular albinism and impaired platelet aggregation. Prostacyclin and its analogues used for the treatment of diseases. First and foremost are ischemic events that occur due to arteriosclerotic occlusion or vascular stenosis. For example, the very rare Raynaud’s syndrome, also known as white finger disease, can be treated with prostacyclin to mask the intermittent spastic constriction of vessels in the fingers or toes by the vasodilatory properties of the tissue hormone.
