Enkephalin in Human Physiology and Pain Regulation

The answer to the question of what is enkephalin can be found within the body itself as it is internally produced hormones. The enkephalins are ligands generated by the body. Enkephalin is a pentapeptide that helps the body regulate nociception. Since the enkephalin hormone is produced internally and binds to the body's opioid receptors, they are referred to as endogenous ligands. Enkephalins suppress painful stimuli in the spinal cord by reacting with various receptor sites on sensory nerve endings. With the knowledge of what is enkephalin, let us go ahead and understand the enkephalin function and working in our body. 

Working of Enkephalin 

Enkephalins are made when the precursor molecule pro-enkephalin is cleaved to produce either met-enkephalin or leu-enkephalin. The gene for pro-enkephalin is made up of three exons separated by two introns. In humans and other animals, specifically mammals, pro-enkephalin processing produces six copies of met-enkephalin and one copy of leu-enkephalin. Enkephalins are found in many parts of the brain, the spinal cord, and the adrenal medulla. Enkephalins found in plasma are thought to come mainly from the adrenal medulla. Biodegradation of enkephalins occurs by hydrolysis, which cleaves the pentapeptide at the Tyr-Gly connection. Enkephalins and aminopeptidases further break down the molecules into shorter peptides of 2 to 4 amino acids.

Enkephalin is a naturally occurring peptide that is produced by neurons and the cells in the central nervous system and the adrenal medulla respectively and has potent painkilling properties. The smallest of the molecules with pain killing or opiate activity are enkephalins, which are pentapeptides with the consensus Tyr-Gly-Gly-Phe-Xaa series. Several Met-enkephalin analogues had increased activity in the hippocampus during a stress response, while Leu-enkephalin analogues and somatostatins were downregulated. Enkephalins are pain-transmitting proteins present in the thalamus of the brain and certain parts of the spinal cord. These naturally occurring morphine-like substances are released by nerve endings in the central nervous system also called CNS and the adrenal medulla. Enkephalins bind to opiate receptors and cause pain to be released in a regulated manner. Leu-enkephalin is an endogenous agonist for the opiate alkaloids-stimulated receptors. It affects the CNS in a variety of ways, including the neuroendocrine hypothalamus. The brain, as well as the cells of the adrenal medulla, contain high levels of enkephalins. 

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Enkephalin Structure

Enkephalin Function in Body

There is multiple enkephalin function in the body and the degree of effect can vary depending on the amount of enkephalin production which varies from individual to individual. 

• The gonadal function is also regulated by leu-enkephalin that has the amino acid sequence Tyr-Gly-Gly-Phe-Leu.

• Met-enkephalin with the amino acid sequence Tyr-Gly-Gly-Phe-Met is involved in pain perception modulation, memory and emotional control.

• Regulates food and liquid intake.

• Immune system regulation, among other things. Met-enkephalin has immunomodulatory properties in a variety of cell types. Upregulation of CD8 and T cells, inhibition of regulatory T cell function, stimulation of macrophage phagocytosis, increased proliferation of CD4 and T-helper 1 cells, and stimulation of the natural killer cell response are some of the effects. 

• It also affects the motility of the digestive system and gastric and pancreatic secretion and carbohydrate metabolism. 

• It is a neuropeptide and thus acts as a signalling molecule of the brain in the human body. 

• Norepinephrine, a hormone involved in the fight-or-flight response, is released in response to pain, along with endorphins.

• The impact is narrow and limited to a local specific brain region like the hippocampus and the prefrontal cortex that controls the aforementioned functions.

• Enkephalin Opioids have a multifaceted impact on the cardiovascular system, with a short-term effect of lowering heart rate and blood pressure and a longer-term effect of increasing myocardial contraction.

• Experience shows that opioids can be used safely in the treatment of cancer pain, with a lower risk of respiratory depression.

• Mu and delta-opioid receptors, located in the submucosal and myenteric plexus levels, respectively, are the main opioid receptors in the gastrointestinal tract. Activation of mu-opioid receptors causes constipation by inhibiting colon motility and increasing fluid absorption that can be avoided when the enkephalin hormone is secreted and binds to the mu-receptor towards which it has great affinity after the delta receptors.

• By altering neuronal excitability, enkephalins and endogenous opioids slow gastrointestinal motility. The key effect is caused by the inhibition of K⁺ and Ca²⁺ channels, which causes hyperpolarization of the cell and, as a result, prevents conductance of an action potential and the release of neurotransmitters necessary for gut motility.

Conclusion

A better understanding of enkephalins and the ligands, receptors, and signalling pathways that make up the endogenous opioid system could lead to important advancements in the development of therapies for the broad range of physiological processes and organ systems in which these agents are involved. The development of potent analgesic therapies without the deleterious side effects associated with opioidergic agents, as well as the use of met-enkephalin (MENK) in the treatment of various cancers and immune-related diseases, are two areas of research that could yield improved treatments in the near future. The research done in this area can be revolutionary and quite detrimental in the future of science and the body.