Prostaglandins

Prostaglandins are cyclic fatty acid compounds that have hormone-like effects on animals. They are found in the majority of tissues in humans and other animals, and similar molecules have been found in plants. Scientists are increasingly using the term eicosanoids when referring to prostaglandins. The effects of prostaglandins vary considerably in different types of tissue. Some prostaglandins act as vasodilators, relaxing the blood vessels to cause them to dilate, which reduces blood pressure by increasing blood flow. Prostaglandins are also important in the body's ability to form blood clots and secrete gastric acid, and are a factor in the development of inflammation due to the dilation of blood vessels. In women, they stimulate the uterine muscles to contract. They are often used to induce labor.

The body releases prostaglandins as a response to stimuli such as disease, stress, or trauma. The prostaglandins help to protect cells. These compounds are used in treating and preventing blood clots. They are also used to treat asthma, ulcers, and pain.

Background

Swedish physiologist Ulf von Euler discovered prostaglandins in 1935 in a sample of human semen. He believed they were a prostate gland secretion, so he called them prostaglandins. Von Euler, who shared the 1970 Nobel Prize in Physiology or Medicine with two other researchers, found the compounds were present in the seminal fluid and seminal vesicles of most animals. The true origin and function of prostaglandins remained a mystery for decades, however.

Swedish biochemists Sune K. Bergström and Bengt Ingemar Samuelsson and British biochemist Sir John Robert Vane studied prostaglandins during the 1960s and 1970s, and in 1982 won the Nobel Prize for Physiology or Medicine for their work. Bergström first met von Euler in 1945. With his graduate student, Samuelsson, Bergström conducted research on the compounds. He discovered the chemical structure of two prostaglandins, PGE and PGF, and the origin of the compounds. The researchers found that prostaglandins are formed from the progressive conversions of an unsaturated fatty acid, arachidonic acid, caused by the enzyme cyclo-oxygenase. This discovery enabled them to create prostaglandins through a synthetic process, which allowed more scientists to research the compounds.

Samuelsson and Bergström also learned that prostaglandins fall into two primary categories. One branch includes the stable prostaglandins and the thromboxanes and prostacyclins that are formed from cyclic endoperoxides. Thromboxanes and prostacyclins are necessary to help blood thicken and clot. The other branch contains the leukotrienes, which are related to allergic reactions, such as constriction of bronchium.

Vane developed better biological assays, or bioassays, to measure substances in bodily fluids during the early 1960s. This technique helped him find prostaglandins in many organs and tissues throughout the body. The discovery indicated that the compound was not produced in the prostate. In 1969, Vane discovered how aspirin works in treating inflammation and pain. Using guinea pig tissue, he found aspirin obstructs production of prostaglandins that cause inflammation, and learned the compounds could help dissolve blood clots. Aspirin was the most commonly used drug around the world and had been a medical staple since 1899, yet researchers had no idea until late in the twentieth century of the effects it had on the body.

Overview

Stimuli cause the body to release arachidonic acid from phospholipid molecules, which are found in cell membranes. The acid release is affected by a variety of factors, including the enzymes available. The enzyme lipoxygenase causes a chemical reaction, or catalysis, that transforms the arachidonic acid into a leukotriene. The enzyme cyclooxygenase catalyzes the acid into an endoperoxide, which may become prostaglandins, prostacyclins, or thromboxanes. These prostaglandins are not stored in tissues; the body produces them when they are needed. They perform their function quickly, then either move to another part of the body where they are needed or are metabolized almost instantly.

The prostaglandins bind to different types of receptors. When binding to some types, the compounds inhibit reactions, while the same prostaglandin would stimulate a reaction when binding to other receptors.

Prostaglandins play a role in forming and reducing blood clots. Thromboxanes aid in blood clotting by stimulating blood platelets to gather and become sticky, so they cling together and stick to tissue where a plug is needed to stop bleeding. The platelets send out signals to other platelets to get them to join together to form clots. Conversely, prostacyclin inhibits this process. Some drugs, such as aspirin, prevent platelets from signaling one another to stick together. For this reason, doctors often have patients at risk of developing blood clots take a daily aspirin. Platelets are unable to make more of the thromboxane enzyme that encourages clotting.

Clotting processes have been the focus of medical research, such as efforts to prevent heart attacks and strokes, as well as deep vein thrombosis, a life-threatening condition caused by clots that form when blood pools in veins, such as the legs, often due to inactivity. Other research has focused on conditions caused by the body's inability to form blood clots. For example, researchers have found that patients with hemophilia and von Willebrand disease do not produce sufficient amounts of a type of thromboxane that stimulates platelets to clot.

Leukotrienes are important in conditions marked by inflammation. Certain stimuli may cause an increase in leukocytes, or white blood cells, which fight infection. Most white blood cells reside in tissues until they are needed elsewhere in the body, at which time they enter the bloodstream. Allergic reactions also trigger the release of leukotrienes and other inflammatory chemicals to respond to a perceived threat. Leukotrienes can bind with receptors on muscle cells; in patients with asthma, this can cause contraction of windpipe muscles that constricts airways.

Prostaglandins cause pain and swelling. Some cells called phagocytes engulf or ingest harmful substances, such as dead cells and bacteria. This action stimulates production of prostaglandins and other inflammatory chemicals. A large amount of prostaglandin, such as might be released because of injury, can directly affect nerve endings. Nerves can become highly sensitized by even low levels of prostaglandin, which could cause a person to feel pain at the slightest stimuli. Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, are effective pain relievers because they block prostaglandin production by inhibiting Cox-1 and Cox-2 enzymes, which are needed to produce prostaglandins. With less prostaglandin, pain and swelling are reduced. NSAIDs must be taken with care, however, because some prostaglandins also help protect the lining of the digestive tract. Fewer prostaglandins can leave the digestive system open to irritation.

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