They are lipid autacoids derived from arachidonic acid. Both maintain the homeostatic functions and mediate the pathogenic mechanisms, including the inflammatory response.
Prostaglandins (PG) E2 (PGE2) are unsaturated fatty acids of natural origin implicated in various physiological and physiopathological processes that involve organ function.
Unlike most hormones, prostaglandins are not secreted from a gland to transport in the bloodstream and work in specific areas around the body.
Instead, they are made by a chemical reaction where they are needed and can be done in almost every body organ.
They are generated from arachidonate by the action of isoenzymes of cyclooxygenase (COX). Their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including selective ones to inhibit COX-2.
Prostaglandins are part of the way the body treats injuries and illnesses.
Despite the clinical efficacy of nonsteroidal anti-inflammatory drugs, prostaglandins can function both in promoting and resolving inflammation.
The biology of prostaglandin has a possible clinical relevance for atherosclerosis, the response to vascular injury, and aortic aneurysm.
One of the most striking actions of the prostaglandins of the E and A series is their ability to dilate the peripheral blood vessels and, therefore, lower blood pressure.
Alterations may mediate this vasodilatory effect of prostaglandins in the circulating blood levels of the hormones or by changes in the concentration of prostaglandins in the walls of the blood vessels.
Prostaglandins have also been implicated in the regulation of the renin-angiotensin-aldosterone system. In addition, a direct effect of prostaglandins on the modulation of renal blood flow and renal tubular sodium reabsorption has been suggested.
An effect of the prostaglandins to inhibit the action of vasopressin from increasing water permeability in the mammalian collecting duct has also been proposed.
Alternative Names: Prostaglandin D2; prostaglandin E2; Prostaglandin F2; prostaglandin I2 (also known as prostacyclin); a closely related lipid called thromboxane.
Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide.
The hypothesis that parathyroid hormone and carbonic anhydrase inhibitors have a common mechanism or site of action on phosphate reabsorption by the renal tubule was proved by administering parathyroid hormone in the absence and presence acetazolamide in thyroparatiroidectomized dogs.
Micropuncture microanalysis methodologies and recirculation probes were used. In the absence of acetazolamide, parathyroid hormone increased the fractional phosphate supply (and volume) of the proximal tubule from 28 ± 2 to 38 ± 3%, P <0.025, and increased the fractional phosphate excretion from 3.8 ± 1.2 to 19.9 ± 3.7 %, P <0.005 (eight dogs).
In the presence of acetazolamide, parathyroid hormone increased the fractional phosphate (but not volume) supply from the proximal tubule from 50 ± 4 to 58 ± 5%, P <0.025, and increased fractional phosphate excretion of 8.7 ± 2.2 a 31.0 ± 4.3%, P <0.001 (12 dogs).
Therefore, the effects of parathyroid hormone were additive to the maximal inhibition of carbonic anhydrase, indicating that parathyroid hormone and carbonic anhydrase inhibitors have different mechanisms of action on phosphate reabsorption by the tubule renal.
In addition, the reabsorption of phosphate beyond the micropuncture point in the proximal tubule was much more markedly inhibited by parathyroid hormone than by acetazolamide.
Functions of prostaglandins
Prostaglandins are compounds of natural origin that are easily separable from other biologically active substances due to their acidic lipid nature.
Prostaglandins are known to regulate the female reproductive system and are involved in the control of ovulation, the menstrual cycle, and the induction of labor.
They are divided into four series, the A, B, E, and Alpha series, which differ in the characteristic 5-member ring structure. Prostaglandins play a role in the following reproductive functions:
The manufactured forms of prostaglandins, prostaglandin E2 and F2, can be used to induce (tear) labor.
It has also been proposed that prostaglandin A is the natriuretic hormone, the circulating hormone that controls the reabsorption of sodium by the kidney.
Lee and Ferguson’s experiments in which prostaglandins inhibited the uptake of pulmonary arterial hypertension by the bark of renal cortex in vitro support this view.
Prostaglandins are also involved in:
- The transfer of fluids in the intestine.
- As causative agents of diarrhea accompany the medullary carcinoma of the thyroid or tumors of the neural crest.
- In the reduction of blood pressure in humans with essential hypertension.
- In the metabolism of fatty acids, including lipolysis.
- As mediators of the inflammatory response.
Additional research on prostaglandins will establish the validity of the prostaglandins’ proposed physiological or pathological functions.
Prostaglandins play a vital role in the generation of the inflammatory response. Its biosynthesis increases significantly in the inflamed tissue and contributes to developing the cardinal signs of acute inflammation.
Although the proinflammatory properties of the individual prostaglandins during the acute inflammatory response are well established, their role in the resolution of inflammation is more controversial.
This review will discuss the biosynthesis and response to prostaglandins and the pharmacology of their blockade to orchestrate the inflammatory response, with particular attention to cardiovascular disease.
The opposite effects that thromboxane and prostacyclin have on the width of blood vessels can control the amount of blood flow and regulate the response to injury and inflammation.
Prostaglandins are also involved in regulating contraction and relaxation of the intestine and respiratory tract muscles.
Biosynthesis of prostaglandins
Prostaglandins and thromboxane A2 (TXA2), collectively called prostanoids, are formed when arachidonic acid (AA), a 20-carbon unsaturated fatty acid, is released from the plasma membrane by phospholipases (PLA) and metabolized by sequential actions of prostaglandin G / H synthase, or cyclooxygenase (COX), and respective synthases.
There are four primary bioactive prostaglandins generated in vivo: prostaglandin (PG) E2 (PGE2), prostacyclin (PGI2), and prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α).
They are produced ubiquitously. Generally, each type of cell generates one or two dominant products and acts as a mediator of autocrine and paracrine lipids to maintain local homeostasis in the body.
The level and profile of prostaglandin production during an inflammatory response change drastically. The production of prostaglandins is generally deficient in non-inflamed tissues but increases immediately in acute inflammation before leukocyte recruitment and infiltration of immune cells.
The production of prostaglandins depends on the G / H synthases, colloquially known as COX, bifunctional enzymes that contain cyclooxygenase activity, and peroxidase that exist as different isoforms called COX-1 and COX-2.
COX-1, expressed in most cells, is the predominant source of prostanoids that serve as maintenance functions, such as gastric epithelial cytoprotection and homeostasis.
COX-2, induced by inflammatory stimuli, hormones, and growth factors, is the most crucial source of prostanoid formation in inflammation and proliferative diseases, such as cancer.
However, both enzymes contribute to the generation of self-regulating and homeostatic prostanoids, contributing to the release of prostanoids during inflammation.
PGH2 is produced by both isoforms of COX and is the common substrate for a series of specific isomerase and synthase enzymes that produce PGE2, PGI2, PGD2, PGF2α, and TXA2.
COX-1 is preferably, but not exclusively, coupled with thromboxane synthase (TXS), prostaglandin F synthase, and cytosolic isozymes (c) prostaglandin E synthase (PAGES).
COX-2 prefers prostaglandin I synthase (PGIS) and microsomal isozymes (m) of PAGES, which are often produced together with COX-2 by cytokines and tumor promoters.
The profile of prostanoid production is determined by the differential expression of these enzymes within the cells present in the sites of inflammation. For example, mast cells generate predominantly PGD2 while macrophages produce PGE2 and TXA2.
In addition, alterations in the profile of prostanoid synthesis after cell activation may occur. While resting macrophages produce TXA2 over PGE2, this relationship changes to favor the production of PGE2 after the activation of bacterial lipopolysaccharide (LPS).
How are prostaglandins controlled?
The chemical reaction that produces prostaglandins involves several steps; The first step is carried out by an enzyme called cyclooxygenase. There are two main types of this enzyme: cyclooxygenase-1 and cyclooxygenase-2.
When the body is functioning normally, the basal levels of prostaglandins are produced by cyclooxygenase-1. When the body is injured (or inflammation occurs in anybody area), cyclooxygenase-2 is activated and produces additional prostaglandins, which helps the body respond to the injury.
The prostaglandins carry out their actions by acting on specific receptors; At least eight different prostaglandin receptors have been discovered.
The presence of these receptors in different organs throughout the body allows the other actions of each prostaglandin to be carried out, depending on which receptor they interact with.
Prostaglandins are very brief, and the body breaks them down quickly. They only carry out their actions near where they occur; This helps regulate and limit your actions.
What happens if I have too many prostaglandins?
High levels of prostaglandins occur in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain, and fever. This is an integral part of the body’s normal healing process.
However, this natural response can sometimes lead to excessive and chronic production of prostaglandins, contributing to various diseases by causing unwanted inflammation.
This means that drugs, which specifically block cyclo-oxygenase-2, can treat conditions like arthritis, heavy menstrual bleeding, painful menstrual cramps, and certain types of cancer, such as colon and breast cancer.
Discoveries are being made about cyclooxygenases that suggest that cyclooxygenase-2 is not only responsible for the disease but has other functions.
Anti-inflammatory medications, such as aspirin and ibuprofen, work by blocking the action of cyclooxygenase enzymes and thus reducing prostaglandin levels.
This is how these drugs work to relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and, therefore, can be used to prevent the coagulation of unwanted blood in patients with heart disease.
What happens if I have too few prostaglandins?
The manufactured prostaglandins can increase the levels of prostaglandins in the body under certain circumstances. For example, the administration of prostaglandins can induce labor at the end of pregnancy or abortion in the case of an unwanted pregnancy.
They can also treat stomach ulcers, glaucoma, and congenital heart disease in newborn babies.