Neurotransmitters and Receptor Theory

These are the discussion post I need to respond to on the first day and second day These are the instructions regarding what the response should consist of
Respond to at least two of your colleagues on two different days in one of the following ways:
1. If your colleagues’ posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained.
2. If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective.

 

Moses Kamuri
Week 2 discussion Main post.
COLLAPSE
Foundational Neuroscience
Foundational Neuroscience explores the organization and functioning of the nervous system. Mental health practitioners must understand how medications trigger neurotransmitters release to bind specific receptors for favorable patient response.

The Agonist-to-Antagonist Spectrum of Action of Psychopharmacologic Agents

Traditional receptor theory assumed that receptors are dormant unless activated by a ligand. Ligands act as agonists or antagonists. Agonists bind and activate specific receptors and have affinity and intrinsic efficacy, while antagonists block the action of agonist or specific receptors’ release, have affinity and zero intrinsic efficacy (Berg and Clarke, 2018). The agonist spectrum can be classified into four types: agonist, partial agonist, antagonist, and inverse agonist. Agonist opens the channel to maximal amount and frequency allowed by the binding site, and Partial agonist does not reach full binding capacity. In the presence of full agonists, it acts as an antagonist, decreasing the full agonist’s ability to activate the receptor (Berg and Clarke, 2018). The inverse agonist affects an agonist’s efficacy by binding receptors at the same receptor binding site (Berg and Clarke, 2018). Further, it produces the opposite effect as an agonist reducing the receptor signal. Thus, the presence of a partial or inverse agonist may impact the efficacy of psychopharmacologic treatment.

The Actions of G Couple Proteins and Ion Gated Channels

The opening or closing of postsynaptic ion channels is accomplished in different ways by two broad families of the receptor protein. The receptor in one family is called the ionotropic receptor, which is directly linked to ion channels. These receptors have two functional domains: the extracellular site that binds neurotransmitters and the membrane-spanning domain to form ion channels (Alexander et al., 2017). Inotropic receptors combine transmitter binding and channel functions into one single molecular entity called ligand -gated ion channels. Some of these receptors have four or five individual protein subunits that play a part in the pore of ion channels (Alexander et al., 2017).

The metabotropic receptor is the second family of the neurotransmitter, whereby the movement of ions in this scenario depends on one or more metabolic steps. Whereby there are no ion channels in these receptors, so channels are affected by the intermediate activation molecules called G-proteins; thus, metabotropic receptors are also called G-protein coupled receptors. Metabotropic receptors are monomeric proteins having an extracellular domain for neurotransmitter binding and an intracellular domain for binding to G- proteins. The binding of neurotransmitters to metabotropic receptors activates G proteins. It dissociates from the receptor and interacts directly with ion channels or binds to make other effector proteins. For instance, the enzymes make intracellular messengers to open or close ion channels. Thus, G protein work as transducers that couple neurotransmitter binding to the regulation of postsynaptic ion channels (Camicia et al., 2018).

 

Jane Smith
Discussion – Week 2
COLLAPSE
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments.

Nutt et al. (2017) said that drugs prescribed by psychologists follow the basic concepts of receptor agonism and antagonism, but most drugs are antagonism. The article continued to say that antagonist drugs block the effect of a neurotransmitter such as dopamine in treating schizophrenia or the serotonin transporter in the case of serotonin reuptake inhibitors for depression. Inverse agonists produce the opposite effect of an agonist. That is, if it binds to the same receptor as an agonist, it creates the opposite effect of that agonist (Berg and Clarke 2018). A partial agonist produces less stimulation than a full agonist (Zhang et al., 2020).

Compare and contrast the actions of g couple proteins and ion gated channels.

According to Yang et al. (2021) g protein-coupled receptors are located on the cell membrane and represent the largest protein family encoded by the human genome. They also said that g couple protein helps regulate several body functions, such as regulating growth and releasing hormones. They have seven-transmembrane protein properties with diversified downstream signaling pathways, making them attractive for drug development (Yang et al., 2021).

Ion gated channels are large transmembrane proteins based on their electrochemical potential. They provide a pathway for ions to diffuse at a high rate across the cell membrane ( Roux B 2017). Roux 2017 continued to say that ion channels provide a passage for ions to diffuse rapidly according to electrochemical potential.

Explain how the role of epigenetics may contribute to pharmacologic action.

Epigenetics is the change in gene expression without altering the DNA sequence but the chromosome (Al Aboud et al., 2020). The article continued to say that genes can be turned on or off using epigenetics. With recent improvements in the genome, pharmacology is fighting diseases not in the conventional way of drug-receptor mechanism but manipulating genes to fight diseases, especially in the treatment of cancer. One advantage of epigenetics in pharmacology is that epigenetics variations can be the underlying cause of a disease. If this happens to target one protein of the many pathways can be ineffective. Epigenetic mechanisms tackle more than one gene or multiple proteins. (Stefanska & MacEwan 2015).

Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.

One area of concern is drug-to-drug interaction. Niu et al. (2019) said that drug interactions occur “when another drug alters the pharmacological effect of one drug in a combination regimen.” When prescribing medication, clinicians should be aware of any other drugs the patient is taking, including street drugs, illegal drugs, or designer drugs. This is because most drugs have structures or similar pharmacological profiles that may cause adverse reactions or even death.

This is also my prior discussion post along with the instructions you completed for me a few days ago
Post a response to each of the following: I’m including this to help guide the discussion reply

1. Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments.
2. Compare and contrast the actions of g couple proteins and ion gated channels.
3. Explain how the role of epigenetics may contribute to pharmacologic action.
4. Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.
Foundational neuroscience
Neuroscience is the scientific study of the brain and its effect on human behavior and thinking. The brain controls the voluntary and involuntary actions of the body. It also controls human behavior through their thinking. The brain plays a big role in the function of other organs of the body such as the heart, lungs, liver, skin, and kidneys. The PNP should understand the physiology of the brain so that to understand the mode of action in psychopharmacology. During the treatment of psychiatric disorders, it is important to understand the concepts of neuroscience.
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments.
An agonist is a chemical that occupies and binds to the receptors and triggers the receptor to produce a biological response. They also increase the proportion of the activated receptors. Full agonists produce a maximum biologic response (Josephy-Hernandez, et al, 2017). Full agonists are generally efficient and have independent of potency. For example, epinephrine is a full agonist because it produces maximum effects when administered. Partial agonist produces lesser results than expected. They have less than 100% of the expected result despite maximum dose administration. Examples of partial agonists are opioids. An antagonist blocks the action of the agonist at the receptor thus inhibiting a chemical or biological reaction. The antagonist blocks the receptors from producing the desired result (Josephy-Hernandez, et al, 2017). For example, fluphenazine is an antipsychotic medicine that antagonizes the dopaminergic D1 and D2 receptors blocking the production of hypothalamic hormones.
Compare and contrast the actions of g couple proteins and ion gated channels.
G couple proteins GPCRs are integral membrane proteins that are used by cells to convert extracellular responses including response to hormones, neurotransmitters, olfaction, and taste signals (Sriram, K., & Insel, P. A. 2018). The GPCRs work by binding to the hormones, neurotransmitters, and growth factors to initiate a cellular response. Ion gated channels are transmembrane proteins of excitable cells that allow a flux of ions to pass only under defined circumstances. These channels are either voltage-gated by sodium channel neurons or ligand dated by the acetylcholine receptors of the cholinergic synapses (Van Hook, et al, 2019). The ion gated channel pull and bonds to the agonist changing the protein while g coupled proteins are used by the cells to convert intracellular signals into responses.
Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics regulate gene activity by switching off the gene activity or activating the gene activity. Epigenetics plays a major role in the phenotypic activity of the cell in diseases such as cancer and neurodegenerative disorders such as Alzheimer’s disease (Delgado-Morales, et al, 2017). Epigenetics modify gene expressions after drug administration to counteract the disease states in humans. Therefore, epigenetics proves to be effective in treating psychiatric and neurodegenerative disorders to its ability to modify gene expressions.
Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.
A psychiatric mental health nurse practitioner should have basic knowledge of the concepts of foundational neuroscience. Understanding the basic function of agonists, inverse agonists, partial agonists, and antagonists prevents co-administration of drugs that agonize and antagonize at the same receptors. For example, in treating a patient with a depressive mood disorder, prescribing antipsychotics such as fluphenazine worsens the depressive mood because it antagonizes the dopaminergic D1 and D2 receptors depressing the release of the hypothalamic hormone.

The Role of Epigenetics to Pharmacologic Action

Epigenetics studies changes that influence the phenotype without causing changes in the genotype or genetic control not resulting from an individual’s DNA sequence. This is the study of inheritable but reversible changes in gene expression without any modifications of primary DNA sequence (Bufill et al., 2020). Epigenetic mechanisms, for instance, circulating MiRNAs, are used as diagnostic markers. Epigenetic regulation of gene activity is important in maintaining a normal phenotypic activity of cells and treating diseases such as cancer and neurodegenerative disorders such as dementia, Alzheimer’s, and schizophrenia. New classes of medication are currently used to regulate epigenetic mechanisms to manage diseases in individuals (Bufill et al., 2020).

How This Information May Impact Medications Prescribing

Information on agonist, antagonist, partial, and inverse agonist may influence the medications one prescribes. It is critical to collect patient history on the medications that a patient is currently taking to assess any possible interaction between the four agents. For instance, buprenorphine, an opioid partial agonist taken by an opioid (full opioid agonist) addict, yields a partial effect, helping deter opioid abuse and detoxification upon binding. Hence, prescribing buprenorphine is appropriate for patients with an opioid addiction problem.

References
Alexander, S. P., Striessnig, J., Kelly, E., Marrion, N. V., Peters, J. A., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., & Davies, J. A. (2017). The concise guide to pharmacology 2017/18: Voltage-gated ion channels. British Journal of Pharmacology, 174, S160-S194. https://doi.org/10.1111/bph.13884

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: inverse agonism and functional selectivity. International Journal of Neuropsychopharmacology, 21(10), 962-977. https://dx.doi.org/10.1093/ijnp%2Fpyy071

Bufill, E., Ribosa-Nogué, R., & Blesa, R. (2020). The therapeutic potential of epigenetic modifications in Alzheimer’s disease. Alzheimer’s Disease: Drug Discovery, 151-164. https://doi.org/10.36255/exonpublications.alzheimersdisease.2020.ch9

Camicia, F., Celentano, A. M., Johns, M. E., Chan, J. D., Maldonado, L., Vaca, H., Di Siervi, N., Kamentezky, L., Gamo, A. M., Ortega-Gutierrez, S., Martin-Fontecha, M., Davio, C., Marchant, J. S., & Rosenzvit, M. C. (2018). Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes. PLOS Neglected Tropical Diseases, 12(2), e0006267. https://doi.org/10.1371/journal.pntd.0006267

Delgado-Morales, R., Agís-Balboa, R. C., Esteller, M., & Berdasco, M. (2017). Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clinical epigenetics, 9(1), 1-18.
Josephy-Hernandez, S., Jmaeff, S., Pirvulescu, I., Aboulkassim, T., & Saragovi, H. U. (2017). Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm. Neurobiology of disease, 97, 139-155.
Sriram, K., & Insel, P. A. (2018). G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs?. Molecular pharmacology, 93(4), 251-258.
Van Hook, M. J., Nawy, S., & Thoreson, W. B. (2019). Voltage-and calcium-gated ion channels of neurons in the vertebrate retina. Progress in retinal and eye research, 72, 100760.

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Solution

Discussion response 1

 

Hey Moses Kamuri!

Thanks for sharing your content with us; it is very educational. As you mentioned in your post, agonists and antagonists govern the activity of psychopharmacologic medicines. When an agonist binds to a receptor, it causes a response, while antagonist binding suppresses neurotransmission (Berg & Clarke, 2018). The effectiveness of different kinds of agonists, such as full agonists, inverse agonists, and partial agonists, varies. Inverse agonists, for instance, have a negative efficacy.

While agonists are universally assumed to elicit a positive reaction, their spectrum of activity varies significantly; for example, an inverse agonist’s effect is the opposite of a full agonist’s action. A medicine’s impact also differs substantially depending on the type of receptor. Binding an inotropic ligand to an inotropic receptor, for example, promotes the opening of the ion channel, whereas binding a metabotropic receptor starts a chain reaction via G-protein (Sriram & Insel, 2018).

References

Sriram, K., & Insel, P. A. (2018). G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs?. Molecular Pharmacology, 93(4), 251-258.

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: inverse agonism and functional selectivity. International Journal of Neuropsychopharmacology, 21(10), 962-977. https://dx.doi.org/10.1093/ijnp%2Fpyy071

 

 

 

Discussion response 2

 

Hello, Jane Smith!

Thanks for sharing your insightful and well-written post with us. The post is exciting, and I genuinely enjoyed reading it. The interaction of medication with receptors causes both therapeutic and harmful effects. Agonist binding causes a response, whereas antagonist binding suppresses neurotransmission (Josephy-Hernandez et al., 2017). The action of various agonists, such as partial agonists, inverse agonists, and full agonists, varies substantially, which characterizes the agonist-antagonist spectrum.

As you mentioned in your post, G-couple proteins are integral membrane receptors. The cell uses G-couple proteins to transform extracellular signals instead of ligand-gated ion channels. I liked how you expanded on the role of epigenetics in pharmaceutical activity. The epigenetic notion has had a significant impact on medical prescription and development. This has aided in illuminating various undesirable effects that frequently occur when using standard pharmacotherapy (Delgado-Morales et al., 2017).

References

Delgado-Morales, R., Agís-Balboa, R. C., Esteller, M., & Berdasco, M. (2017). Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clinical epigenetics, 9(1), 1-18.

Josephy-Hernandez, S., Jmaeff, S., Pirvulescu, I., Aboulkassim, T., & Saragovi, H. U. (2017). Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm. Neurobiology of Disease, 97, 139-155.

 

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