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- Hormone
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- prostanoid
- prostacyclin
Prostaglandin
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What are prostaglandins?
Prostaglandins are potent, hormonelike substances that play pivotal roles in inflammation, blood flow, and other physiological processes. They are synthesized from unsaturated fatty acids, such as arachidonic acid, which contain a cyclopentane ring.
Prostaglandins are produced in almost every human and animal tissue. They can act as autocrine or paracrine agents, stimulating reactions in the same or nearby tissues.
Different biological activities of prostaglandins are related to structural differences. Some raise blood pressure, while others lower it; some can stimulate a reaction in one tissue and inhibit the same reaction in another. Drugs like aspirin and ibuprofen inhibit prostaglandin synthesis and are effective at suppressing inflammation.
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Where in the body are prostaglandins made?
Prostaglandins are produced in almost every tissue in humans and other animals. These compounds are synthesized from arachidonic acid, a fatty acid within cell membranes, and are created and released in response to various stimuli.
Prostaglandins can act locally on the cells that produce them (autocrine function) or on nearby tissues (paracrine function). They influence various biological activities, including inflammation, blood pressure regulation, smooth muscle contraction, and other processes.
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What do prostaglandins do in the body?
Prostaglandins are potent, naturally occurring lipid compounds that act as chemical messengers with diverse effects in humans and animals. They regulate essential physiological processes and mediate inflammatory and immune responses.
Prostaglandins operate in an autocrine fashion, stimulating reactions in the same tissue in which they are synthesized, and in a paracrine fashion, stimulating reactions in local tissues near where they are synthesized. Prostaglandins are involved in inflammation, blood flow, vasodilation, blood clotting, and smooth muscle contraction. Because prostaglandins stimulate uterine muscle contraction, inhibitors of prostaglandin synthesis, such as ibuprofen, can successfully treat menstrual cramps.
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How do prostaglandins affect pain and inflammation?
Prostaglandins are potent compounds found in almost every tissue that play a pivotal role in inflammation, which is characterized by redness, heat, pain, and swelling. These changes are due to the widening of local blood vessels, increasing blood flow to the affected area. The blood vessels also become more permeable, leading white blood cells to move from the blood to the inflamed tissues.
NSAIDs (nonsteroidal anti-inflammatory drugs) reduce inflammation and relieve pain by inhibiting the synthesis of prostaglandins. Drugs like aspirin or ibuprofen that inhibit prostaglandin synthesis can effectively suppress inflammation.
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How are medicines like ibuprofen related to prostaglandins?
Ibuprofen, like aspirin, is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits the synthesis of prostaglandins, which are molecules that cause inflammation and pain. Prostaglandins are synthesized in blood vessel walls and act locally to relax blood vessels, increasing blood flow, which results in inflammation following tissue injury. By blocking prostaglandin production, ibuprofen and similar drugs can suppress inflammation and relieve pain.
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Besides pain and inflammation, what other body processes involve prostaglandins?
Prostaglandins are involved in several other body processes besides pain and inflammation. They affect the contraction and relaxation of smooth muscle in the gastrointestinal tract. They can either stimulate or inhibit the contraction of smooth muscles in the intestinal walls and protect the alimentary tract's mucosa from injury.
In women, prostaglandins also play a role in ovulation and stimulate uterine muscle contraction. Prostaglandins can also affect blood pressure by causing the blood vessels to dilate.
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Prostaglandin, any of a group of naturally occurring lipid compounds that act as chemical messengers, having diverse functions and effects in humans and other animals. Prostaglandins are powerful substances that serve to regulate essential physiological processes and that mediate inflammatory and immune responses. Their role as chemical messengers makes them a valuable target for therapeutic interventions, especially those developed for the treatment of pain and inflammation.
Discovery
Prostaglandins were discovered in human semen in 1935 by Swedish physiologist Ulf von Euler, who named them, thinking that they were secreted by the prostate gland. The understanding of prostaglandins grew in the 1960s and ’70s with the pioneering research of Swedish biochemists Sune K. Bergström and Bengt Ingemar Samuelsson and British biochemist Sir John Robert Vane. The threesome shared the Nobel Prize for Physiology or Medicine in 1982 for their isolation, identification, and analysis of numerous prostaglandins.
Synthesis of prostaglandins
Prostaglandins are made up of unsaturated fatty acids that contain a cyclopentane (5-carbon) ring and are derived from the 20-carbon, straight-chain, polyunsaturated fatty acid precursor arachidonic acid.
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Arachidonic acid is a key component of phospholipids, which are themselves integral components of cell membranes. In response to many different stimuli, including various hormonal, chemical, or physical agents, a chain of events is set in motion that results in prostaglandin formation and release. These stimuli, either directly or indirectly, result in the activation of an enzyme called phospholipase A2. This enzyme catalyzes the release of arachidonic acid from phospholipid molecules.
Depending on the type of stimulus and the enzymes present, arachidonic acid may diverge down one of several possible pathways. One enzyme, lipoxygenase, catalyzes the conversion of arachidonic acid to one of several possible leukotrienes, which are important mediators of the inflammatory process. Another enzyme, cyclooxygenase, catalyzes the conversion of arachidonic acid to one of several possible endoperoxides. The endoperoxides undergo further modifications to form prostaglandins, prostacyclin, and thromboxanes. The thromboxanes and prostacyclin have important functions in the process of blood coagulation.
Biological activities of prostaglandins
Prostaglandins have been found in almost every tissue in humans and other animals. Plants synthesize molecules similar in structure to prostaglandins, including jasmonic acid (jasmonate), which regulates processes such as plant reproduction, fruit ripening, and flowering. Prostaglandins are very potent; for example, in humans some affect blood pressure at concentrations as low as 0.1 microgram per kilogram of body weight.
The structural differences between prostaglandins account for their different biological activities. Some prostaglandins act in an autocrine fashion, stimulating reactions in the same tissue in which they are synthesized, and others act in a paracrine fashion, stimulating reactions in local tissues near where they are synthesized. In addition, a given prostaglandin may have different and even opposite effects in different tissues. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds.
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Vasodilation and blood clotting
Most prostaglandins act locally; for instance, they are powerful locally acting vasodilators. Vasodilation occurs when the muscles in the walls of blood vessels relax so that the vessels dilate. This creates less resistance to blood flow and allows blood flow to increase and blood pressure to decrease. An important example of the vasodilatory action of prostaglandins is found in the kidneys, in which widespread vasodilation leads to an increase in the flow of blood to the kidneys and an increase in the excretion of sodium in the urine. Thromboxanes, on the other hand, are powerful vasoconstrictors that cause a decrease in blood flow and an increase in blood pressure.
Thromboxanes and prostacyclins play an important role in the formation of blood clots. The process of clot formation begins with an aggregation of blood platelets. This process is strongly stimulated by thromboxanes and inhibited by prostacyclin. Prostacyclin is synthesized in the walls of blood vessels and serves the physiological function of preventing needless clot formation. In contrast, thromboxanes are synthesized within platelets, and, in response to vessel injury, which causes platelets to adhere to one another and to the walls of blood vessels thromboxanes are released to promote clot formation. Platelet adherence is increased in arteries that are affected by the process of atherosclerosis. In affected vessels the platelets aggregate into a plaque called a thrombus along the interior surface of the vessel wall. A thrombus may partially or completely block (occlude) blood flow through a vessel or may break off from the vessel wall and travel through the bloodstream, at which point it is called an embolus. When an embolus becomes lodged in another vessel where it completely occludes blood flow, it causes an embolism. Thrombi and emboli are the most common causes of heart attack (myocardial infarction). Therapy with daily low doses of aspirin (an inhibitor of cyclooxygenase) has had some success as a preventive measure for people who are at high risk of heart attack.
Inflammation
Prostaglandins play a pivotal role in inflammation, a process characterized by redness (rubor), heat (calor), pain (dolor), and swelling (tumor). The changes associated with inflammation are due to dilation of local blood vessels that permits increased blood flow to the affected area. The blood vessels also become more permeable, leading to the escape of white blood cells (leukocytes) from the blood into the inflamed tissues. Thus, drugs such as aspirin or ibuprofen that inhibit prostaglandin synthesis are effective in suppressing inflammation in patients with inflammatory but noninfectious diseases, such as rheumatoid arthritis.
Smooth muscle contraction
Although prostaglandins were first detected in semen, no clear role in reproduction has been established for them in males. This is not true in women, however. Prostaglandins play a role in ovulation, and they stimulate uterine muscle contraction—a discovery that led to the successful treatment of menstrual cramps (dysmenorrhea) with inhibitors of prostaglandin synthesis, such as ibuprofen. Prostaglandins also play a role in inducing labor in pregnant women at term, and they are given to induce therapeutic abortions.
The function of the digestive tract is also affected by prostaglandins, with prostaglandins either stimulating or inhibiting contraction of the smooth muscles of the intestinal walls. In addition, prostaglandins inhibit the secretion of gastric acid, and therefore it is not surprising that drugs such as aspirin that inhibit prostaglandin synthesis may lead to peptic ulcers. Prostaglandin action on the digestive tract may also cause severe watery diarrhea and may mediate the effects of vasoactive intestinal polypeptide in Verner-Morrison syndrome, as well as the effects of cholera toxin.