Targets and Receptors in the Treatment of Conditions in the Gastro-Intestinal System

2021-07-13 06:57:02
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The gastrointestinal system is a system in human beings and other animals that is tasked with the digestion and absorption of energy and nutrients and expels the waste products of the digestion process (Hall, 2015). This system consists of the mouth, esophagus, stomach and the intestines.  This system is home to thousands of different bacteria in the gut of the flora. The digestive system releases hormones from hormones to help in the regulation of the digestive process which includes gastrin, secretin, cholecystokinin among others (Hall, 2015).

A receptor is a protein that has the capacity to receive chemical signals from outside the cell. A cellular response will occur when a chemical signal bind to the receptor (Dockray, 2014). A receptor has the capacity to recognize and respond to the endogenous chemical signal. In another word, the receptor will be used as a drug target that is enzymes, transporters, and ion channel (Dockray, 2014). Receptors mainly will be classified according to where they are found. For example, there are transmembrane, hormone receptors and enzyme-linked hormone receptors. The enzymes found inside the cells will include the cytoplasmic and nuclear receptors. In a cell with many receptors, each receptor will bind to a ligand of a particular structure and not all ligands. When the binding occurs it will activate or inhibit the receptors associated biochemical pathway (Dockray, 2014).

Targets and receptors in the treatment of conditions in the Gastro-Intestinal System

Below are some of the receptors that take part in the treatment of the Gastrointestinal system:-

1. Ghrelin and Motilin receptors

A condition commonly observed in the diabetic patient, Gastroparesis is when there is a delay in the emptying of the gastric without the presence of a mechanical obstruction (Papachristodoulou, 2014). This condition affects approximately 40% of patients with diabetes type 1 and 30% of patients with diabetes type 2. The common symptoms of diabetic gastroparesis will include nausea, vomiting, bloating, and constipation (Papachristodoulou, 2014). Ghrelin receptor agonists have been trialed for the treatment of diabetic gastroparesis because of their ability to increase gastric emptying, but with mixed results; however, relamorelin, a ghrelin agonist, reduced nausea and vomiting in patients with this disorder (Papachristodoulou, 2014) .

The main function of the two enzymes in the digestive system is to increase appetite and inhibit gastric migrating myoelectric complex. These enzymes also have the function to prevent nausea. Ghrelin receptor is used in the treatment of diabetic gastroparesis as it has the ability to increase gastric emptying. These enzymes also have a role in preventing and treating constipation (Papachristodoulou, 2014).

2. G-protein coupled receptors

This is receptors that are tasked to detect outside the cell and activate signal transduction pathways. These receptors are involved in many diseases and are targeted by approximately 40% of all medicines. The prevalence of obesity globally has been on the increase and that of type two diabetes has also been on the rise (Sanger, 2016). Lifestyle modification and weight reduction are one of the most effective preventions and control strategies. Unfortunately, it is very difficult to cut weight naturally making it necessary for the availability of medication that can aid in reducing weight (Sanger, 2016). Targeting the G-coupled receptors in the metabolic tissues has been viewed recently as a target for an antidiabetic compound. This receptor is a target for the formation and development of new drugs to successfully treat type 2 diabetes (Sanger, 2016).

3. Fatty acids and mineral receptors

This is also referred to as the nutrients sensing receptors which will include the fatty acid receptors, calcium-sensing receptors, and zinc sensing receptors (Deloose, 2016). These receptors play an important role in regulating the gastrointestinal system functions. The fatty acids and mineral receptors regulated the gastric and neuroendocrine functions, the mortality of the gastrointestinal system, the ion transport and the growth of cells. In the recent past, scientists have stated that receptors can be promising therapeutic target for the treatment of the gastrointestinal disorders such as inflammatory bowel diseases, colorectal cancer, metabolic syndrome, and diarrheal diseases (Deloose, 2016).

4. Dopamine receptors

This receptors main function is to regulate the gastrointestinal motility (Lismaa, 2013). In most cases, the motility in the upper gut is inhibited by these receptors. Additionally, these receptors also play an important role when it comes to the stimulation of the motility in the colon. These receptors affect the motility of the gastrointestinal system by mediating the muscle relaxation and by inhibiting the release of acetylcholine (Lismaa, 2013)

5. Histamine receptors

These are receptors that are involved in the immune responses as well as regulating functions in the gut, the brain, spinal cord and the uterus (Ley, 2014). They have a part to play in the inflammatory response and mediate itching in the body. Due to this, the receptors have been known to useful in the body especially when it comes to the body functions which are not limited to the following; vasodilatation and fall in blood pressure, affects the nasal mucous membrane, sleep-wake regulations, gastric acid release, protective effects, sexual function among others (Ley, 2014).

This receptor has been found to impact three major functions that are regulating the gastrointestinal motility, enhancing gastric acid production and alteration of the mucosa ion secretion. This receptor also has the function of regulating food and water intake and the feeding rhythm in general (Ley, 2014). These histamines have an important role in nociception, an autoimmune disorder, colon cancer and allergy. Diarrhea is sometimes caused by the overproduction of histamines by the mast cells (Ley, 2014).

6. Opium receptors

This is used mainly used in ant diarrheal management for many years. When they are introduced the opium peptide activated the opioid receptors that control motility and secretion. As an outcome gastric emptying will be inhibited, sphincter tone will be increased, the stationary motor pattern will be inducted, and peristalsis ensues will be blocked (Ganellin, 2013). The opioid receptors can also cause inhibition of fluid secretion which will, in the end, because constipation which is one of the most commonly observed effects. In this case, laxatives can be used to resolve constipation (Ganellin, 2013). Moreover, it has been observed that the peripherally restricted opioid receptor antagonists sometimes tend to act as prokinetic drugs in their own right manner. The action of opioid receptors can be therapeutically be exploited in acute and chronic diarrhea as well as bowel syndrome that is mainly associated with diarrhea (Ganellin, 2013).

7. Motilin and motilin receptors

This is a brain-gut peptide that affects functions of the gastrointestinal system. The level of these receptors is increased in patients living with ulcerative colitis and Crohn's disease (Byrne, 2015). There is a relationship between motilin receptor genotype and the susceptibility to inflammatory bowel diseases (Byrne, 2015). This may not only lead to the further characterization of motilin receptor subtypes and aid the development of safe and selective motilin receptor agonists and antagonists, useful for the treatment of GI disorders but may also give a new dimension to the role of motilin in human physiology (Byrne, 2015).

 

References

Beaulieu, J.M., Espinoza, S. and Gainetdinov, R.R., 2015. Dopamine receptorsIUPHAR review 13. British journal of pharmacology, 172(1), pp.1-23.

Byrne, C.S., Chambers, E.S., Morrison, D.J. and Frost, G., 2015. The role of short chain fatty acids in appetite regulation and energy homeostasis. International journal of obesity (2005), 39(9), p.1331.

Deloose, E., Vos, R., Corsetti, M., Depoortere, I. and Tack, J., 2015. Endogenous motilin, but not ghrelin plasma levels fluctuate in accordance with gastric phase III activity of the migrating motor complex in man. Neurogastroenterology & Motility, 27(1), pp.63-71.

Deloose, E., Vos, R., Janssen, P., Van den Bergh, O., Van Oudenhove, L., Depoortere, I. and Tack, J., 2016. The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway. The American journal of clinical nutrition, 103(3), pp.730-737.

Dockray, G.J., 2014. Gastrointestinal hormones and the dialogue between gut and brain. The Journal of physiology, 592(14), pp.2927-2941.

Ganellin, C.R. and Parsons, M.E. eds., 2013. Pharmacology of histamine receptors. Elsevier.

Hall, J.E., 2015. Guyton and Hall Textbook of Medical Physiology E-Book. Elsevier Health Sciences.

 

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