General Principles of Peptide Pharmacology

Peptides are chains of amino acid molecules linked with the peptide bond. The establishment of the peptide bond takes place with the condensation reaction between the amino-terminal and the carboxyl-terminal of two amino acids releasing water molecules.

The arrangement of the amino acid molecules in the peptide chain is in a predefined order. This enabled the proper folding of the polypeptide chain resulting in a tertiary and quaternary structure that serves as a protein complex.

The protein complex has the characteristic presence of an activation site and other grooves in the structure that makes it function as a biological enzyme. The activity of certain enzymes results in the degradation of the protein and forms varying peptides. These peptide molecules act as hormones and biological messengers and contribute to the development of the response from the body. 

The study of the human response related to the application of the peptides as the biological messenger is termed peptide pharmacology. 

Opioid peptides

Opioids are the receptors located in the brain, spinal cord and digestive tract. These are G-protein coupled receptors and have the presence of the transmembrane domain and the extracellular loop in the structure. The loop serves as the receptor pocket to bind the opioid ligand and mediate signalling. 

The opioid ligands peptide molecules can be given as endogenous opioid peptides and the exogenous opioid peptides.

Endogenous Opioid peptide

The opioid peptides are the short amino acid sequences that are coded by the human genes and participate in the signalling. These peptides are encoded by the pre-proenkephalin A or pro-opiomelanocortin gene precursor and have functions related to the nervous system. 

The primary endogenous opioid peptides synthesised are:

Enkephalin

These are the pentapeptides and are derived mainly in the body by the binding to the opioid receptor. The major function of the enkephalin is found to be nociception regulation in the body.

Endorphins

These peptides are found to be present as the neuropeptides and have storage in the pituitary gland. The major function of these peptides is to increase the sense of pleasure and reduce the feeling of pain.

Dynorphin

These are the class of neuropeptides encoded by the human genome. With its binding to the kappa opioid receptor, dynorphins regulate the mood of an individual. They are invoked with their function in the emotional control of stress, along with learning and memory.

Nociceptin

This is an opioid peptide with 17 amino acids and is found to be involved in the binding with nociceptin opioid receptors known as ORL1 receptors. The binding mediates the function as the control of brain activity.

Endorphins

These are neurotransmitters with the ability to work on the central nervous system, and the binding of the peptide with the receptor forms the relief in the pain sensation as well as adds the feeling of pleasure.

Exogenous Opioid peptide

These are the neurotransmitters that are found to be synthetically produced while binding to the opioid receptors, similar to the endogenous peptides. These peptides are derived from different origins, such as plant-derived morphine or food-derived opioid peptides such as casomorphin and lactoferrin. 

Neuropeptides as the mediators of the immune response

The meditation to the immune response is the reaction of the immune system in the presence of stimuli. The neuropeptides are the mediators or ligands that bind to the receptors present on the neurological cell and help in the modulation of the immune response, such as pain-relieving processes.

The neuropeptides have an effect on the central nervous system and the peripheral nervous system. 

Types of Peptide Mediators

The peptide mediators with their repose to the peripheral nervous system can be given as:

Substance P

It is the peptide of 11 amino acid chains with the conserved carboxyl-terminal sequence of Phe-X-Gly-Leu-Met-NH₂ amino acids. The substance P peptide is given to have immunological importance for the localised area such as the skin, gastrointestinal and respiratory tract. 

The binding of the peptide with the G protein-coupled receptor forms the basis for the development of the pharmacological changes and the mediation of the immune response. The peptide is also involved in vasodilation, causing an increase in nitric oxide production by the endothelial cells.

CGR peptide or CGRP

Calcitonin Gene-Related Peptide is just a 37-amino-acid chain that exists in two forms in humans: alpha and beta. The synthesis of cAMP is caused by the interaction of these peptides with the central nervous system and the peripheral nervous system. It has been discovered to enhance blood flow.

Functions of Peptides in the human body

Apart from being a part of the immune response and the mediator for the peripheral and the central nervous system, there are multiple physiological roles of peptides. Some of the functions of peptides in the human body are given below:

Peptides as Hormones

The locally synthesised water-soluble peptides are considered hormones with their activity of binding to the specific receptor site. The role of peptide hormones is found to be extended to the growth, survival and functionality of the target tissue. 

Some of the examples include serotonin, insulin, and glucagon.

Peptides in Signalling Cascade

The synthesis of the peptides is formed with the mRNA sequence and has the specificity for the protein molecules. The binding of the protein and the peptides is found to activate or deceive various signalling cascades in the body.

Peptides as First Line of Defence

The first line of defence is the role played by the immune system in encountering the entry of the foreign body. It is comprised of several antimicrobial peptide molecules that have binding for the specific microbe and thereby fight against the invasion with the formation of the complex, reducing pathogenicity.

Peptides in Wound Repair

The presence and the synthesis of the endogenous peptides at the site of the wound act to induce cell differentiation and the bacteriolysis process. The biological process with the activation of the growth factor and the tissue matrix facilitates wound healing.

Conclusion

The peptides are the small chain of amino acids with the formation inside the body as well as synthetic synthesis. The peptides found inside the body are termed endogenous peptides, while derived peptides are termed exogenous peptides. Peptide receptors are present in the nervous system and are termed opioid receptors. Peptides, with the mediation to the binding at the protein receptors, form the basis for the various physiological responses, including immune response as the first line of defence, action as hormones, with the involvement in the signalling cascade and wound repair.