G-protein-coupled receptors, also called GPCRs, form the largest receptor family among cell surface proteins 1. This receptor family is large in size and very diverse, especially in mammalian genomes 2. In simple terms, GPCRs are used for cellular communication 1. These receptors still need extensive research since they are such a large, diverse group. More so, continued research can benefit humans when it comes to pharmaceuticals.
GPCRs are key when it comes to cells converting external signals into the correct intracellular signals 1. There is more than 800 GPCRs within the human genome. They are responsible for many of our everyday experiences. For example: some our senses (taste, vision, and smell), “fight-or-flight” responses through our sympathetic nervous system, “rest-and-digest” through our parasympathetic nervous system, and metabolism 1. Cellular communication between cells is a necessity. For example, GPCRs are targeted by scientist and/or industries that are interested in pharmaceuticals.
For G-protein-coupled receptors, ligand binding is the initial step for signals to be transferred 2. A ligand is a chemical that is released from one cell and binds to another cell via receptors 3. GPCRs can bind with an abundance of ligands. For example: photons, ions, amino acids, odorants, eicosanoids, neurotransmitters, peptides, proteins, pheromones, and hormones 1. Photons are “a unit of intensity of light at the retina” 4. An ion is an atom that has net charge, positive or negative 3. Amino acid is defined as an organic molecule that contains an amine group and a carboxyl group, and it is used to build proteins 3. Odorants signal the presence of food, fire, or predators through small molecules that we ge...
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...osensory receptors. http://www.ncbi.nlm.nih.gov/pubmed/19575682 Accessed 28 January 2014.
6. Merriam-Webster. Peptide. http://www.merriam-webster.com/dictionary/peptide
Accessed 28 January 2014.
7. Saito, Toshiyuki; Bunnett, Nigel W.. Protease-Activated Receptors. NeuroMolecular Medicine,
2005. Volume 7. Pages 79-99.
8. Ni, Y. G.; Miled, R.. Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac). Proc. Natl. Acad. Sci., March 1997. Volume 94. Pages 2036-2040.
9. The Nobel Prize in Chemistry 2012. Nobel Media AB, 2013. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/
Accessed 28 January 2014.
10. Brumfield, Ben. Americans win Nobel Prize in chemistry for revealing gateway to cells. CNN,
October 11, 2012. http://www.cnn.com/2012/10/10/world/sweden-nobel-prize-chemistry/ Accessed 9 February 2014.
G-protein-linked receptors are protein receptors, located in the plasma membrane of a cell, that work with G-proteins to activate a cell-signaling pathway. These receptors are structured similarly in most organisms, with seven α helices and specific loops for binding sites for signal molecules and G-proteins. When a signal molecule from the extracellular fluid attaches to the signal-binding site it activates the G-protein-linked receptor by changing its shape. When this happens, the G-protein, loosely attached to the cytoplasmic side of the cellular membrane, attaches to its binding side on the receptor protein. The inactive G-protein becomes activated when GDP is displaced by GTP, a molecule similar to ATP. When the signal molecule is released, the G-protein diffuses along the cell membrane and attaches to an inactive enzyme. This newly activated enzyme triggers the cellular response. When the protein detaches itself from the enzyme, it releases a phosphate group turning GTP back into GDP, making the G-protein inactive once again.
Of the chemical neurotransmitter substances, serotonin is perhaps the most implicated in the treatment of various disorders, including anxiety, depression, obsessive-compulsive disorder, schizophrenia, stroke, obesity, pain, hypertension, vascular disorders, migraine, and nausea. A major factor in the understanding of the role of 5-HT in these disorders is the recent rapid advance made i...
The entire process starts off when an agonist involved is bound to receptors specific to it, expressed on the endothelial cell surface, activating enzymes like phospholipase C (PLC) directly through vascular endothelial growth factor receptors (VEGFR) or by thrombin or histamine through G protein coupled receptors (GPCR).
An analogy that fits very well with the study of the endocrine system is that of a message in a bottle. We can think of the body as a river, and a specific hormone may be a bottle containing a message. The organs or glands mentioned above would manufacture the “bottles'; (hormones) that would be released into the river (blood stream). If there were no receptor sites for the hormones in the body, then they would continue to flow along the river and probably not make their destination. However, there are systems of receptor sites that enable specific hormones to bind in specific places. Structure also plays a major role in determining which hormones are able to bind to which receptors.
Not surprisingly, serotonin is implicated in a broad range of serotonin disorders like depression, schizophrenia, and Parkinson's disease (3).. Serotonin deficiencies have been one of the factors to blame for ailments such as anorexia, bulimia, obsessive compulsive disorders, migraines, social phobias and schizophrenia. (9). (12). I am not taking a stance that serotonin has its hand in all of these different pots, but after the research that I have completed for this paper, I feel comfortable talking about serotonin in reference to depression. No one can say for certain what exactly "causes" depression. But in this paper, I hope to give further insight into serotonin's specific role as a possible predeterminant for major depression and some hopes for those suffering from this illness.
Serotonin is a "neurotransmitter which is responsible for mood, hunger sleep" (www.herbsnow.com/sotm.htm). The website, medquest pharmacy claims that 5-HTP works by increasing the amount of serotonin produced in the brain. And in fact, according to Gastpar and Wakelin (1998), 5-HTP is a known precursor to serotonin which has been proven in many studies. Serotonin levels are supposed to have a direct effect on a persons mood (www.medquwestpharmacy.com/5-htp.htm). In fact antidepressant drugs approved by the FDA, such as Prozac, are said to work by increasing the amount of serotonin available to the brain(www.biosyenrgy.com/5htp.htm).
Accentuates the affinity of the recognition site for GABA by inducing conformational changes that make GABA binding more efficacious.
Schizophrenia is a complicated, mostly permanent psychological disorder involving a disturbances in the relation amongst thought, emotions, and behaviour, leading to defective perception, inappropriate actions and feelings, withdrawal from reality. The National Mental Health Commission makes 10 recommendations, including reducing the use of restraint, seclusion and involuntary treatments. Recommendation 6 states, “There must be the same national commitment to safety and quality of care for mental health services as there is for general health services.”
Depression can result from a physical disease, a mental illness, or it can be a recurring reaction of the body. According to the National Institute of Mental Health, major depressive illnesses are often the result of imbalances in neurotransmitters in the brain. It is these critical chemicals that send messages between nerve fibers and control mood (Creamer, 3). Older anti-depressants worked on three different neurotransmitters, serotonin, norepinepherine, and dopamine. However, it has been found that serotonin is the specific chemical in the brain that controls moods. Its job is to carry an impulse from one nerve fiber to the next. Serotonin is released by the nerve into the space between nerve fib...
Similarly, anti-depressive medications also act upon serotonin receptors in the brain, switching them on or off. It is believed that many psychological disorders stem from an imbalance of serotonin and dopamine. Common treatments for depression include SSRI’s (selective serotonin reuptake inhibitors), which increases serotonin in the brain to combat the deficit from the disorder.
The receptors involved in serotonin are 5-HT pre and postsynaptic receptors. Understanding the mechanism of serotonin aids in various treatments for depression. For example, understanding the levels of cerebrospinal fluid regarding serotonin has significantly aided scientists in understanding the root cause for depression. These levels are much lower in depressed individuals, as well as depressed individuals who attempted suicide (Holtzeimer et al., 2006). In addition to lower cerebrospinal fluid metabolites of serotonin, abnormalities with serotonin binding and reduced amounts of tryptophan have also lead to an understanding of the causes of depression.
Stress is a way of responding to demands that are presented. Stress can either be good and motivate or be bad, such as when there is too much and the body cannot handle it. For both physical and psychological stress the Hypothalamic-pituitary-adrenal (HPA) axis is involved in the response. The HPA axis becomes activated when cortisol levels are increased, such as when stress levels increase (de Kloet, Joëls, & Holsboer, 2005). Glucocorticoid receptors (GCR) are affected by increased cortisol levels due to their high affinity to bind when the cortisol levels are intermediate to high. Furthermore the GCRs are involved in the termination of the stress response (de Kloet et al., 2005).
Psychotherapy and antidepressant drugs are usually the most common method used together to treat depression. The most common antidepressant drugs that are used: Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline) that have been used to treat serotonin, while Effexor (venlaxafine) and Remeron (mirtazapine) have been used to treat serotonin and norepinephrine. The antidepressant medications that are given are classified into different areas that affect different neurotransmitters in particular ways. Serotonin and norepinephrine are both used to ease depression by affecting neurotransmitters used to communicate between brain cells. The current treatments of psychotherapy and antidepressant drugs are failing to help people who have resilient characteristics that leave many patients lost and helpless. Current medications used to treat depression can take about two to six weeks after taking a therapeutic dose of the drug to see improvement, but many claim to feel better in few days. In those two to six weeks there can be many variables that can stray a person to show signs of improvement. The current drugs being used have been
Proteins are considered to be the most versatile macromolecules in a living system. This is because they serve crucial functions in all biological processes. Proteins are linear polymers, and they are made up of monomer units that are called amino acids. The sequence of the amino acids linked together is referred to as the primary structure. A protein will spontaneously fold up into a 3D shape caused by the hydrogen bonding of amino acids near each other. This 3D structure is determined by the sequence of the amino acids. The 3D structure is referred to as the secondary structure. There is also a tertiary structure, which is formed by the long-range interactions of the amino acids. Protein function is directly dependent on this 3D structure.