Prostaglandin

Chemical structure of prostaglandin E₁ (PGE)₁).

The prostaglandins are a group of substances of a lipid nature derived from 20-carbon fatty acids (eicosanoids), which contain a cyclopentane ring and constitute a family of cellular mediators, with diverse effects, often conflicting. Prostaglandins affect and act on different body systems, including the nervous system, smooth muscle, blood, and the reproductive system; They play an important role in regulating various functions such as blood pressure, blood coagulation, the allergic inflammatory response, and the activity of the digestive system.

History and name

The name prostaglandin comes from the prostate gland. When prostaglandins were first isolated from seminal fluid in 1935, they were believed to be part of prostate secretions. In 1971, it was discovered that acetylsalicylic acid (aspirin) and its derivatives can inhibit the synthesis of prostaglandins. Biochemists Sune Karl Bergström, Bengt Samuelsson and John Robert Vane received the Nobel Prize in Physiology and Medicine together in 1982 for their research on prostaglandins.

Synthesis of prostaglandins

They are synthesized from essential fatty acids by the action of different enzymes such as cyclooxygenases, lipoxygenases, cytochrome P-450, peroxidases, etc. Cyclooxygenase gives rise to prostaglandins, thromboxane A-II, and prostacyclin (PGI₂); lipoxygenase gives rise to the acids HPETEs, HETE, and leukotrienes; cytochrome P-450 generates HETEs and hepoxides (EETs). The pathway by which arachidonic acid is metabolized to eicosanoids depends on the tissue, the phospholipase A2, the stimulus, the presence of endogenous and pharmacological inducers or inhibitors, etc.

Function of prostaglandins

Prostaglandins must exert their effect on the cells of origin and the adjacent ones, acting as autocrine and paracrine hormones, being destroyed in the lungs. The actions are multiple and some have practical utility, such as PGE1, which is used clinically to keep the ductus arteriosus open, in children with congenital heart disease (alprostadil) and for the treatment or prevention of gastroduodenal ulcer (misoprostol). PGE2 (dinoprostone) is used as oxytocin in induction of labor, expulsion of the dead fetus, and treatment of hydatidiform mole or spontaneous abortion.

The functions of prostaglandins can be summarized in five points:

1. They intervene in the inflammatory response: vasodilatation, increased permeability of the tissues allowing the passage of the leukocytes, antiplateletizer, stimulus of nerve endings of pain, etc.
2. Increased secretion of gastric mucus, and decrease of gastric acid secretion.
3. They provoke the contraction of smooth musculature. This is especially important in the uterus of the woman. In the human semen there are small amounts of prostaglandins to favor the contraction of the uterus and as a result the promotion of sperm to uterine tubes (phalopion tubes). Likewise, they are released during menstruation, to favor the detachment of the endometrial. Thus, menstrual pains are often treated with prostaglandin release inhibitors.
4. They are involved in the regulation of body temperature.
5. They control the drop in blood pressure by favoring the elimination of substances in the kidney.

Prostaglandins and nonsteroidal anti-inflammatory drugs (NSAIDs)

Since prostaglandins (PGs) participate in inflammatory responses by stimulating pain nerve endings, nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, work by inhibiting cyclooxygenase and thus PG production. On the other hand, prostaglandins are responsible for maintaining the integrity and proliferation of the gastric mucosa, by ensuring an adequate blood supply. The gastric mucosa is one of the stomach protection mechanisms against aggressive agents such as hydrochloric acid and pepsin. Thus, NSAIDs, by inhibiting PGs, leave the gastric mucosa vulnerable to stomach acid and increase the risk of erosions and ulcers.

Types

Table of comparison of the types of prostaglandins prostacyclin I2 (PGI₂), prostaglandin E2 (PGE₂) and prostaglandin F2α (PGF_2α >).

Vascular physiologic function

Prostaglandins have an effect on renal cortical vascular resistance, producing an increase in renal cortical blood flow with the consequent increase in intracellular volume and decrease in peripheral resistance. In this way, together with the hormone ADH and aldosterone, they regulate blood pressure hormonally. The use of any non-steroidal anti-inflammatory drug (NSAID) has the accompanying effect of an increased risk of cardiovascular events (CVR), with the exception of aspirin, which at a dose of 75 mg PO. a day could have a protective effect, its use not being devoid of the classic adverse gastrointestinal side effects (ulcers, bleeding...), and to a lesser degree, perhaps Meloxicam would also have few harmful effects on CVR. NSAIDs, especially in combination with some other type of medication (ACEI, etc.), can have negative effects on kidney function, both acute and long-term. As with all medications, the effects of one NSAID vary from person to person, mainly due to what is now known as pharmacogenetic differences.

Prostaglandins and baldness

US scientists found that levels of the protein prostaglandin D synthase were elevated in hair follicle cells located in bald patches on the scalp, but not in hairy areas, raising the possibility of developing a treatment for stop or even reverse hair thinning and subsequent baldness. As revealed in the journal Science Translational Medicine, drugs that attack this process are already in development. The research could lead to a cream to treat baldness.

Prostaglandins and cancer

Two main enzymes are involved in the synthesis of prostaglandins: cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). In certain pathological processes such as inflammations and neoplasms, there is an overexpression of the COX-2 enzyme, which catalyzes prostaglandins such as PGE2 that stimulates angiogenesis and tumor progression. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, reduce the risk of cancer, such as breast, colon, and prostate cancer. It was speculated that selective COX-2 inhibitors, such as celecoxib as well as sulindac, would maintain this action, although this has yet to be confirmed in clinical trials. [^{missing references}]