Glutamate
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Glutamatergic neurotransmission involves glutamate, the major excitatory neurotransmitter in the brain. There are two pathways for glutamate synthesis from precursors and multiple receptor types including NMDA, AMPA, KA, and metabotropic receptors. The different receptor subunits provide diversity in function. Glutamate signaling is involved in many brain pathways and clinical implications include roles in schizophrenia, Parkinson's disease, and drug mechanisms of action.
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Glutamate muztaba
1) The document presents information on glutamate and glycine, two important neurotransmitters in the central nervous system.
2) Glutamate is the major excitatory neurotransmitter in the brain and is synthesized from glucose or glutamine. It acts through ionotropic and metabotropic receptors.
3) Glycine is another neurotransmitter that acts as an obligatory co-agonist along with glutamate at NMDA receptors, allowing calcium influx and excitation of postsynaptic neurons. Excess glutamate activation can lead to excitotoxicity and neuronal damage in various neurological conditions.
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Glutamate is the major excitatory neurotransmitter in the central nervous system. It acts through ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated ion channels composed of NMDA, AMPA, and kainate receptor subtypes that allow cation influx. Metabotropic receptors are G protein-coupled receptors divided into three groups based on sequence homology and signaling pathways. Glutamate receptors play important roles in normal neurotransmission but excessive activation can lead to excitotoxicity involved in various neurological disorders.
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3) Glycine is another neurotransmitter that acts as an obligatory co-agonist along with glutamate at NMDA receptors, allowing calcium influx and excitation of postsynaptic neurons. Excess glutamate activation can lead to excitotoxicity and neuronal damage in various neurological conditions.
L-Glutamate
My presentation on neurotransmitter glutamate. References from Comprehensive textbook of psychiatry 9th edition and Stahl's essential psychopharmacology 4th edition.
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This slideshare is about what is autocoid,and differences between harmone and autocoid and had expalined about an example which is an autocoid and also an chemical messenger.and it is also known as happy harmone.
5HT widely distributed in:
GIT enterochromaffin cells (90%)
myenteric plexus where it serves as a prokinetic agent
As a neurotransmitter in CNS
platelets where it diffuses inside from plasma by active transport, and is released at the site of damage after platelet aggregation,
In lungs, bone marrow, pineal gland (as a precursor of melatonin)
5- HT is then stored in 5-HT containing cells such as enterochromaffin cells and neurons as co-transmitter together with various peptide hormones such as somatostatin, vasoactive intestinal peptide and substance P
5-HT is stored within storage vesicles, and its uptake at the vesicular membrane by vesicular monoamine transporter (VMAT-2) is inhibited by reserpine.
Degradation occurs through oxidative deamination by MAO, to 5-hydroxyindole acetaldehyde followed by its oxidation to 5-hydroxyindole acetic acid (5-HIAA)
5- HIAA is excreted in urine
Gaddum and Picarelli (1957) classified 5-HT receptors into musculotropic (D type) and neurotropic (M type) on the basis of their blockade by Dibenzyline (phenoxybenzamine) and Morphine.
5- HT Receptors: there are seven main types (5-HT1, to 5- HT7) of serotonin receptors. Of these, 5-HT1, and 5- HT2, are subdivided further. With a total of 14 (types plus subtypes) receptors.
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5-HT1 : Auto receptors; inhibit serotonergic neural activity in brain.
5-HT1A—present in raphe nuclei and hippocampus; buspirone (antianxiety) may act through these receptors.
5-HT1D/1B—Constricts cranial blood vessels and inhibits release of inflammatory neuropeptides in them; sumatriptan (antimigraine) acts through these receptors.
5-HT2A : Previously D type receptor; most important post junctional receptor mediating direct actions of 5-HT like vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; ketanserin blocks these receptors.
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- GPCRs are classified into families based on sequence homology and functional similarity. The largest family is rhodopsin-like receptors which have 7 transmembrane domains.
- GPCRs are activated via conformational changes in the transmembrane domains, primarily involving movements of "microswitches" that allow the receptor to activate associated G proteins and downstream signaling.
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This document provides an overview of glutamate, the main excitatory neurotransmitter in the central nervous system. It discusses that glutamate is widely distributed in the CNS and involved in many behavioral and physiological functions. It also describes the different types of glutamate receptors, including ionotropic AMPA, kainate, and NMDA receptors and metabotropic receptors. Excitotoxicity is explained as the pathological process by which nerve cells are damaged from excessive stimulation by glutamate leading to calcium overload. The physiological and pathological roles of the different receptors are also summarized.
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SEROTONIN.pptx
This slideshare is about what is autocoid,and differences between harmone and autocoid and had expalined about an example which is an autocoid and also an chemical messenger.and it is also known as happy harmone.
5HT widely distributed in:
GIT enterochromaffin cells (90%)
myenteric plexus where it serves as a prokinetic agent
As a neurotransmitter in CNS
platelets where it diffuses inside from plasma by active transport, and is released at the site of damage after platelet aggregation,
In lungs, bone marrow, pineal gland (as a precursor of melatonin)
5- HT is then stored in 5-HT containing cells such as enterochromaffin cells and neurons as co-transmitter together with various peptide hormones such as somatostatin, vasoactive intestinal peptide and substance P
5-HT is stored within storage vesicles, and its uptake at the vesicular membrane by vesicular monoamine transporter (VMAT-2) is inhibited by reserpine.
Degradation occurs through oxidative deamination by MAO, to 5-hydroxyindole acetaldehyde followed by its oxidation to 5-hydroxyindole acetic acid (5-HIAA)
5- HIAA is excreted in urine
Gaddum and Picarelli (1957) classified 5-HT receptors into musculotropic (D type) and neurotropic (M type) on the basis of their blockade by Dibenzyline (phenoxybenzamine) and Morphine.
5- HT Receptors: there are seven main types (5-HT1, to 5- HT7) of serotonin receptors. Of these, 5-HT1, and 5- HT2, are subdivided further. With a total of 14 (types plus subtypes) receptors.
5-HT Receptors Location: 5-HT, receptors are located mainly in CNS. They function as inhibitory presynaptic receptors (auto receptor) and belong to the family of G-protein coupled receptors linked to adenylate cyclase
5-HT1 : Auto receptors; inhibit serotonergic neural activity in brain.
5-HT1A—present in raphe nuclei and hippocampus; buspirone (antianxiety) may act through these receptors.
5-HT1D/1B—Constricts cranial blood vessels and inhibits release of inflammatory neuropeptides in them; sumatriptan (antimigraine) acts through these receptors.
5-HT2A : Previously D type receptor; most important post junctional receptor mediating direct actions of 5-HT like vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; ketanserin blocks these receptors.
5-HT3 : Previously M type receptor; depolarizes neurones by gating cation channels; elicits reflex effects of 5-HT—emesis, gut peristalsis, bradycardia, transient hypotension, apnoea, pain, itch; ondansetron (antiemetic) acts by blocking these receptors.
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5-HT is involved in the regulation of mood, behaviour, sleep, depression, pain perception, sexual activity, thermoregulation
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AN OVERVIEW ON THE INVOLVMENT OF SEROTONIN (5-HT) IN CENTRALLY AND PERIPHERALLY MEDIATED PHYISIOLOGICAL FUNCTIONS
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The document discusses the glycine receptor, a ligand-gated chloride channel protein that is the major inhibitory neurotransmitter in the adult central nervous system. It exists as a pentameric protein composed of alpha and beta subunits that surround a central pore. Glycine binding activates the receptor, allowing chloride ion influx that hyperpolarizes the neuron. Disorders involving glycine receptor mutations can cause startle disease or non-ketotic hyperglycinemia. The receptor has many ligands but is antagonized primarily by strychnine.
GABA, glutamate receptors and their modulation
This document provides an overview of glutamate and GABA, their receptors and therapeutic applications. It discusses the synthesis, storage, release and termination of glutamate and GABA in the central nervous system. It describes the ionotropic and metabotropic glutamate receptors and GABAA and GABAB receptors. It also discusses conditions associated with glutamate like seizures, neurodegenerative diseases and stroke. Finally, it outlines current and upcoming therapeutic agents that target glutamate and GABA receptors and their uses, mechanisms and adverse effects.
Neurotransmitter - Dopamine
Dopamine is a neurotransmitter that plays a key role in reward processing, motor control, and addiction. It acts through two families of G protein-coupled receptors and is synthesized and transported via specific pathways in the brain, notably the mesolimbic pathway associated with reward. Dopamine neurons fire in response to unexpected rewards and encode reward prediction errors, helping to reinforce rewarding behaviors. Imbalances in dopamine signaling are implicated in various disorders like addiction, Parkinson's disease, and schizophrenia.
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Recent advances also mentioned like H3 & H4 receptors role in cognitive impairment etc.
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This document provides an overview of G-protein coupled receptors (GPCRs) and their role in cell signaling. It discusses the history and structure of GPCRs, how they interact with G-proteins and secondary messengers like cAMP and IP3 to activate intracellular signaling pathways. These pathways regulate key cellular processes and are targets for drug development to treat diseases. The document also categorizes different classes of GPCRs and summarizes the mechanisms and physiological roles of various secondary messenger systems like cAMP, IP3, and ion channels in signal transduction.
G protein coupled receptor(gpcr)
This document discusses G-protein coupled receptors (GPCRs):
- GPCRs are the largest family of transmembrane receptors and play important roles in human senses and physiology. They respond to a wide range of ligands.
- GPCRs are classified into families based on sequence homology and functional similarity. The largest family is rhodopsin-like receptors which have 7 transmembrane domains.
- GPCRs are activated via conformational changes in the transmembrane domains, primarily involving movements of "microswitches" that allow the receptor to activate associated G proteins and downstream signaling.
Neurohumoral transmission in central nervous system
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Serotonin is a monoamine neurotransmitter synthesized from tryptophan. It is found extensively in the gastrointestinal tract and in serotonergic neurons in the central nervous system. Serotonin receptors include 5-HT1-7 and are involved in various physiological functions like mood, appetite, sleep, and pain perception. Imbalances in the serotonergic system are associated with disorders like depression, anxiety, schizophrenia, and impulse control disorders. Drugs that affect the serotonergic system include SSRIs, SNRIs, triptans, 5-HT3 antagonists, buspirone, and MAOIs.
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This document discusses various cognitive enhancers and their mechanisms of action. It covers categories of enhancers like racetams, cholinergics, AMPAkines, and nootropic vitamins. Specific substances are explained, such as piracetam, aniracetam, citicoline, modafinil, and phenibut. Their impacts on neurotransmitters like acetylcholine, glutamate, dopamine, and GABA are described. Conditions they may help with include Alzheimer's, ADHD, depression, and neurodegenerative diseases. Their mechanisms involve increasing blood flow, neurotransmission, neuronal metabolism, and acting as antioxidants.
Importance of si rna and microrna
siRNA and miRNA both regulate gene expression, but through different mechanisms. siRNA targets specific gene sequences, while a single miRNA can regulate many genes. siRNA is found in plants, fungi, and insects but not mammals, which have other antiviral responses. miRNA are small non-coding RNAs around 22 nucleotides long that bind to mRNA to repress translation or promote degradation. They play important roles in development, physiology, and disease when their expression is dysregulated.
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Serotonin (5-HT) is synthesized from tryptophan and is found in the intestine, platelets, and brain. It is stored in nerve endings and platelets then released and reabsorbed by serotonin transporters. There are multiple types of serotonin receptors which mediate its various actions in the cardiovascular, gastrointestinal, respiratory, and central nervous systems. Serotonin can both constrict and dilate arteries, stimulate smooth muscles and peristalsis, inhibit gastric acid and protect ulcers, and cause pain sensations and hyperventilation when activated.
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Histamine
Histamine is a biogenic amine found in many tissues that is involved in allergic and inflammatory processes as well as gastric acid secretion and neurotransmission. It is synthesized and stored in mast cells and basophils and released during allergic reactions. Histamine exerts its effects through four receptor subtypes (H1-H4), with H1 and H2 receptors having drugs that target them clinically. H1 receptor antagonists are used to treat allergic rhinitis, chronic urticaria, and motion sickness, while H2 receptor antagonists suppress gastric acid secretion. New drugs targeting H3 and H4 receptors may provide treatments for neurological and inflammatory conditions, respectively.
Serotonin
Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter synthesized from tryptophan that has various roles in both the peripheral and central nervous systems. It acts through multiple receptor subtypes and is involved in processes like mood, appetite, vomiting, and pain perception. Drugs that affect the serotonin system are used to treat conditions such as depression, anxiety, migraine, and nausea.
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Glutamate and glycine are important neurotransmitters in the central nervous system. Glutamate is the primary excitatory neurotransmitter and is synthesized from glucose or glutamine. It acts through ionotropic and metabotropic glutamate receptors. The three main ionotropic receptor subtypes are NMDA, AMPA, and kainate receptors. NMDA receptors require both glutamate and glycine to open the ion channel. Metabotropic glutamate receptors are G protein-coupled and modulate intracellular signaling pathways. Glycine is also a neurotransmitter and is required as a co-agonist for NMDA receptor activation, playing a role in excitatory neurotransmission.
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G-protein coupled receptors (GPCRs) are integral membrane proteins that interact with extracellular signaling molecules and activate intracellular signaling pathways. There are over 1000 known GPCRs that are classified into three main families based on sequence homology. Upon agonist binding, GPCRs activate heterotrimeric G proteins located on the intracellular side of the cell membrane, initiating downstream signaling cascades such as the cAMP pathway or phospholipase C pathway. GPCRs play key roles in many physiological processes and are the targets of about 40% of all modern medicinal drugs.
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G protein–coupled receptors (GPCRs) are a family of receptors that detect signals outside cells and transmit signals inside. They have seven transmembrane domains and exist only in eukaryotes. When an external signal binds a GPCR, it activates a G protein, which can then activate second messengers like cAMP or IP3 that trigger intracellular responses. GPCRs help regulate many bodily functions through this signal transduction pathway.
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G-protein coupled receptors (GPCRs) are the largest family of membrane receptors that are linked to intracellular effector proteins via G-protein activation. There are several classes of GPCRs classified based on sequence homology. All GPCRs have seven transmembrane domains and signal through heterotrimeric G proteins. When a ligand binds a GPCR, it activates an associated G protein which then regulates downstream effectors like adenylyl cyclase or phospholipase C. These pathways mediate many physiological processes such as vision, smell, immune response, and neuronal signaling.
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G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors and mediate cellular responses to a wide range of signaling molecules. They signal through trimeric G-proteins, which functionally couple the receptors to target enzymes like adenylyl cyclase. Some G-proteins activate adenylyl cyclase to produce the second messenger cAMP, while others inhibit it. cAMP functions through protein kinase A to regulate metabolism and gene transcription. Cholera toxin causes prolonged cAMP production by permanently activating G-proteins, leading to severe diarrhea.
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It is the major excitatory neurotransmitter in the mammalian central nervoussystem (CNS).
Glutamate in the CNS comes mainly from either glucose(via the Krebs's cycle) or Glutamine, which is synthesized by glial cells and takenupby the neurons.
Responsible for neural communication , memory formation , learning andregulation.
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GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
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The simple dogma that underpins much of our current understanding of GPCRs, namely,
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The document summarizes G protein-coupled receptor (GPCR) signaling. It discusses how different GPCRs are coupled to different G proteins that activate various downstream effectors like adenylyl cyclase, phospholipase C or ion channels. It provides examples of specific GPCRs like beta-adrenergic receptors and muscarinic acetylcholine receptor and their signaling mechanisms. It also describes the role of second messengers like cAMP, IP3 and DAG in GPCR signaling.
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G protein-coupled receptors (GPCRs) are integral membrane proteins that sense molecules outside the cell and activate intracellular signal transduction. They have seven transmembrane domains and couple to heterotrimeric G proteins inside the cell. When agonists bind to GPCRs, it causes a conformational change activating the G protein, which then activates downstream effectors like adenylyl cyclase. This leads to the formation of second messengers like cyclic AMP (cAMP) and diacylglycerol. Mutations in GPCRs and G proteins can cause disease by disrupting signaling, like loss of function mutations resulting in hormone resistance or constitutively active mutations mimicking hormone excess.
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G protein-coupled receptors (GPCRs) are seven transmembrane receptors that activate intracellular signaling pathways through heterotrimeric G proteins. When an agonist binds to a GPCR, it causes a conformational change activating the G protein's α subunit. The activated α subunit then interacts with downstream effectors like adenylyl cyclase or phospholipase C. This leads to the production of second messengers like cAMP or IP3. Mutations in GPCRs and G proteins can cause disease by disrupting signaling, with loss or gain of function mutations associated with various endocrine disorders and cancers.
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Glutamate
- 1. Glutamatergic Neurotransmission Srinath G N N Rao
- 2. Outline Chemistry Pathways Clinical implications
- 4. Two precursors for glutamate synthesis: α-ketoglutarate , glutamine α-ketoglutarate L-Glutamate GDH
- 5. Glutamate Receptor Composition Out In Subunits { NMDAR1 NMDAR2a NMDAR2b NMDAR2c Na++ NMDA K+ Ca++ { GLUR1 GLUR2* GLUR3 GLUR4 Ca++ AMPA Na++ K+ Na++ { GLUR5 GLUR6 GLUR7 KA1 KA2 KA K+ Ca++
- 6. AMPA receptor functional diversity Mixing and matching of subunits (see GABA receptors for examples) Further diversity generated by alternative splicing, editing Flip and flop splice forms desensitize at different rates, both have rapid onset kinetics (gluR2 homomers shown)
- 8. Ion selectivity is modulated by RNA editing Kandel, Schwartz, Jessel (2000) Principles of Neural Science 4ed
- 9. NMDAR
- 12. Metabotropic Glutamate Receptors (mGluR’s) mGluR function: modulatory Class C GPCR, very limited homology to rhodopsin mGluR’s are sub-divided based on sequence similarity Group I ( mGluR1 and mGluR5 )(Gq---PLC) Group II ( mGluR2 and mGluR3 )(Gi---AC) Group III ( mGluR4, mGluR6, mGluR7 and mGluR8 )(Gi---AC)
- 14. Allosteric
- 15. Positive modulator enhances response to glutamate
- 16. Negative modulator suppresses response to glutamateModified : http://www.npsp.com/img/img_mGluR_diag.jpg
- 17. mGlu5 receptor antagonists exhibit the widest and most robust anxiolytic activity (MPEP (2-methyl-6-(phenylethynyl)-pyridine), a highly selective and brain-penetrant mGlu5 receptor antagonist) metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. activation of either mGlu(5) by positive allosteric modulators or stimulation of mGluR(2/3) receptors by agonists may offer new strategy in schizophrenia treatment.
- 18. mGlu7 receptor is prominently expressed in the basal ganglia, its role in restoring motor function in animal models of Parkinson's disease are being tried selective mGlu3 receptor agonists or enhancers are potential candidates as neuroprotective agents in Parkinson's disease, and their use might circumvent the limitations associated with the administration of exogenous GDNF.
- 19. Glycine
- 20. Glycine- from Choline and L-Serine L-Serine Glial cells L-Serine Glycine L-Serine D-Serine D-Serine OH pyruvate LSerT Glial cell SHMT AMPA Na+ THF Racemase Gly DAO GlyT1 3Na+
- 22. Pathways in the brain
- 25. CSTC Loop
- 31. Miscellaneous Estrogen increases glutamate release Serotonin increases glutamate release
- 32. Drugs Memantine-gating of blocked channels and binding to two sites on NMDA receptors PCP Ketamine Topiramate-inhibition of GluR5 kainate receptors could represent a key mechanism underlying the anticonvulsant activity of TPM Drugs in schizophrenia- Glutamate agonists or antagonists? Glycine agonists- d- cycloserine
- 33. References Kaplan & Saddock- CTP 9th ed. Psychopharmacology- Stephen Stahl Psychiatry- Tasman- 3rd ed. Neuroscience- Purves www. Pubmed.com
- 34. Thank you