In humans, TP receptors are present in nearly all kinds of blood vessels, airways and blood platelets, and their main role is to mediate smooth muscle contraction and cause platelet aggregation (IUPHAR, 2009). In mice, they have been found on the thymus, spleen, lungs and CD4+ and CD8+ T cells (IUPHAR, 2009).. IP receptors: The main functions of the IP receptors are vascular smooth muscle relaxation and inhibition of platelet aggregation. They also play a role in counteracting vasoconstriction and platelet activation mediated via TP receptors.
To serve these functions, the IP receptors are mainly found on several tissues including aorta, lung, heart (atrium and ventricle), kidney, etc. (IUPHAR, 2009). In contrast to humans, in mice these have been found on the thick ascending limb of the kidney, the dorsal root ganglion neurons and the thymus (IUPHAR, 2009). FP receptors: In animal models (cats and dogs) FP receptors are found to be widely distributed in smooth muscles where they mediate contraction.
In humans, evidence has shown the presence of these receptors in the eye and myometrium though their presence in several other locations such as the kidney has been proposed (IUPHAR, 2009). What are the structural and functional differences between prostaglandins and thromboxanes? Prostaglandins are prostanoids which were initially isolated from human semen in the 1930s and it was believed that they originate from the prostrate gland, hence the name prostaglandins. Since then, extensive research has shown that prostaglandins are present in virtually all cells of the body and are involved in a variety of functions (Ophardt, 2003).
Prostaglandins are polyunsaturated carboxylic acids and are biochemically synthesized from the fatty acid, arachidonic acid. They consist of a 20-carbon skeleton which also encompasses a cyclopentane ring and two side chains named A and V attached to the ring. The 20-carbon chain can have single, double or triple bonds. Similarly, the cyclopentane ring is found in a variety of different arrangements and the basis of this arrangement prostaglandins are classified into different subtypes varying from A to I.
In addition, all prostaglandins have been shown to have a hydroxyl group on carbon 15 and a trans-double bond at carbon 13 of the alkyl substituent (R2) (Ophardt, 2003). Thromboxane, like the prostaglandins is a member of the family prostanoids. There are two major subtypes of thromboxanes i. e. thromboxane A2 and thromboxane B2. In contrast to prostaglandins, thromboxanes do not possess a cyclopentane ring. Thromboxane A (TXA) contains an unstable bicyclic oxygenated ring structure while thromboxane B has been shown to have a stable oxane ring ((Ophardt, 2003).
Prostaglandins are autacoids i. e. they act locally, as opposed to hormones which circulate in the blood and have distant effects. The mechanism of action of these substances is two-fold. Firstly, secreted prostaglandins bind to specific cell surface G-protein coupled receptors, and lead to an increase in the cAMP levels. Secondly, Prostaglandins function on the nuclear level by binding to nuclear receptors and altering gene expression. Prostaglandins are found in a variety of subtypes, each having different functions.
Most In the GI tract, prostaglandins are believed to have a protective function. This is achieved by the inhibition of gastric acid synthesis and increase in the secretion of protective mucus. They are also involved in causing vasodilatation thereby causing an increase in the blood flow to kidneys (Ophardt, 2003, Mathews, 2000) The main functions of some of the important prostaglandins are discussed below: PGE2 This molecule is known to have a diverse range of functions the most important ones being vasodilation and bronchodilation.
It has also been shown to cause uterine contractions and due to this property, has been used to induce labor. Like all other prostaglandins, PGE2 is involved in the initiation and activation of the inflammatory response. In addition, n important property of this compound is that it is an inhibitor of platelet aggregation (Mathews, 2000) PGF2 As opposed to PGE2, PGF2 is involved in vasoconstriction and bronchoconstriction. It has also been proven to cause smooth muscle contraction, e. g. in the intestinal tract and the uterus (Mathews, 2000). PGI2
This is another important molecule produced by the vascular endothelial cells. It impedes thrombogenesis by inhibiting platelet aggregation which is achieved by increasing the concentration of cellular cyclic AMP. This molecule works in opposition to thromboxane which is a potent promoter of platelet aggregation. The rest of the functions of PGI2 are opposite to those of PGF2 i. e. it inhibits vascular constriction, bronchoconstriction and gastrointestinal and uterine contraction (Mathews, 2000). The mechanism of action and functions of the thromboxanes is different from the prostaglandins.
These molecules bind to G- protein coupled receptors, and as opposed to prostaglandins, lead to a decrease in the intracellular concentration of cAMP. The main role of thromboxanes is in thrombosis i. e. formation of blood clots. This is achieved by inducing and promoting platelet aggregation as this substance is released by activated platelets. In addition to this, thromboxanes are vasoconstrictors and potent hypertensive agents. In the human body, thromboxanes and prostacyclin (a certain subtype of prostaglandins) are present in a balance had have opposing functions of vasoconstriction and vasodilatation (Mathews, 2000).
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