Tissues and cells

Prostanoid receptors were first discovered in the early 1970s when it was shown that many tissues and cells possessed specific high-affinity binding sites for certain prostanoids (Narumiya, 1999). It was later discovered that prostanoids receptors are G-protein-coupled receptors and specific receptors for Thromboxane, PGI, PGE, PGF, and PGD are present on different body cells. These were therefore designated TP, IP, EP, FP and DP, respectively. The EP receptors are further classified into four subtypes: EP1, EP2, EP3 and EP4 each of which has different actions (Coleman, 1990).

The location and functions of various types of prostanoid receptors, in both human and animal models are discussed below: DP1 receptors: In animal models, the presence of DP1 receptors in various locations has been proven. For example, in the rat brain, these receptors are located on the cells of the choroid plexus and leptomeninges, while in the spinal cord these receptors are located in both the ventral and dorsal horns of the lumbar spinal cord.

Similarly, the presence of DP1 receptors on the cells of the rat airway epithelium, stomach, duodenum, ileum and colon (mucous-secreting goblet cells and cuboidal epithelium) has also been demonstrated (IUPHAR, 2009). In the humans, experiments have proven the presence of DP1 receptors on the mucous-secreting goblet cells of the colon, human eosinophils and various locations in the eye including the ciliary, longitudinal and circular ciliary muscles, retinal choroid, iris although their specific functions are largely unknown.

The most important finding has been of the demonstration of these receptors on human platelets where they are believed to cause the stimulation of cAMP accumulation and inhibition of platelet aggregation and in the brain cells, where they may be involved in the regulation of sleep. Other implicated roles of these receptors are the inhibition of histamine release, relaxation of the myometrium, inhibition of superoxide release from neutrophils, regulation of eosinophil apoptosis and the relaxation of pulmonary venous smooth muscle and bronchial smooth muscle (IUPHAR, 2009).

DP2 Receptors: As with DP1 receptors, the presence of DP2 receptors on various rat tissues including the lungs, brain, ovary, spleen, liver, kidney, heart, thymus, spleen and Th1 and Th2 cells. In humans, these receptors are located in the stomach, small intestine, heart, thymus, colon, spinal cord, brain, skeletal muscle, spleen and various types of blood cells including eosinophils and Th2-type lymphocytes. DP2 receptors have been shown to be involved in eosinophil activation, chemotaxis and degranulation, stimulation of cytokine production (IUPHAR, 2009).

EP Receptors: Till date, four subtypes of EP receptors are known viz. EP1, EP2, EP3 and EP4 each of which has different actions. It has been shown that EP1 and EP3 receptors mediate excitatory effects, while EP2 and EP4 receptors mediate inhibitory effects. In humans, EP1, EP2 and EP4 receptors are found in two main organs: the kidney (connecting segments, cortical and medullary collecting ducts, media of arteries, media of afferent and efferent arterioles) and the eye (endothelial and smooth muscle cells of blood vessels of iris, ciliary body, and choroid.

EP3 receptors, in addition to the kidney and eye are also found in the myometrium of the uterus and the thalamus. The functions of EP3 receptors include contraction of smooth muscle, enhancement of platelet aggregation, inhibition of autonomic neurotransmitter release, inhibition of gastric acid secretion, and inhibition of fat cell lipolysis (IUPHAR, 2009).

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 …

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