Target type: biologicalprocess
The controlled release of glutamate by a cell, in which the glutamate acts as a neurotransmitter. [GOC:dph]
Glutamate secretion, a crucial process in neuronal communication, involves a complex interplay of intracellular signaling pathways, vesicle trafficking, and membrane fusion. Here's a detailed breakdown:
1. **Glutamate Synthesis and Packaging:**
- Glutamate, the primary excitatory neurotransmitter in the central nervous system, is synthesized from glutamine by the enzyme glutaminase within presynaptic neurons.
- Synthesized glutamate is then actively transported into synaptic vesicles, small membrane-bound sacs that store neurotransmitters. This transport is mediated by vesicular glutamate transporters (VGLUTs), ensuring high concentrations of glutamate within the vesicles.
2. **Action Potential Arrival and Calcium Influx:**
- When an action potential arrives at the presynaptic terminal, it triggers the opening of voltage-gated calcium channels.
- Calcium ions (Ca2+) rapidly influx into the presynaptic terminal, acting as a critical signal for neurotransmitter release.
3. **Vesicle Docking and Fusion:**
- The influx of Ca2+ initiates a cascade of molecular events leading to the fusion of glutamate-filled vesicles with the presynaptic membrane.
- Synaptotagmin, a Ca2+-binding protein, plays a key role in this process by sensing Ca2+ levels and mediating vesicle docking and fusion.
- Other proteins, including SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), also contribute to the precise docking and fusion of vesicles with the presynaptic membrane.
4. **Glutamate Release into Synaptic Cleft:**
- Upon fusion, the vesicle membrane merges with the presynaptic membrane, releasing glutamate into the synaptic cleft, the narrow space between the presynaptic and postsynaptic neurons.
- This release of glutamate is a rapid and highly regulated process, ensuring precise neurotransmission.
5. **Glutamate Receptor Activation:**
- Glutamate released into the synaptic cleft binds to glutamate receptors on the postsynaptic neuron.
- These receptors, including AMPA, NMDA, and kainate receptors, are ionotropic, meaning they directly open ion channels upon glutamate binding.
- This opening allows ions like sodium and calcium to flow into the postsynaptic neuron, triggering an excitatory postsynaptic potential (EPSP) and ultimately contributing to neuronal signaling.
6. **Glutamate Clearance and Recycling:**
- To ensure precise and efficient neurotransmission, glutamate is rapidly removed from the synaptic cleft after release.
- This removal is achieved by glutamate transporters, which actively transport glutamate back into presynaptic neurons or into surrounding glial cells.
- Glial cells can then convert glutamate back into glutamine, which is transported back to presynaptic neurons, completing the cycle.
7. **Regulation of Glutamate Secretion:**
- Glutamate secretion is tightly regulated by various mechanisms, including presynaptic autoreceptors, feedback loops, and intracellular signaling pathways.
- These mechanisms ensure that glutamate release occurs at appropriate levels and in response to specific neuronal activity, preventing excessive excitation or neurotoxicity.'
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Protein | Definition | Taxonomy |
---|---|---|
ATP-sensitive inward rectifier potassium channel 8 | An ATP-sensitive inward rectifier potassium channel 8 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q15842] | Homo sapiens (human) |
ATP-binding cassette sub-family C member 8 | An ATP-binding cassette sub-family C member 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q09428] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
diazoxide | diazoxide : A benzothiadiazine that is the S,S-dioxide of 2H-1,2,4-benzothiadiazine which is substituted at position 3 by a methyl group and at position 7 by chlorine. A peripheral vasodilator, it increases the concentration of glucose in the plasma and inhibits the secretion of insulin by the beta- cells of the pancreas. It is used orally in the management of intractable hypoglycaemia and intravenously in the management of hypertensive emergencies. Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group. | benzothiadiazine; organochlorine compound; sulfone | antihypertensive agent; beta-adrenergic agonist; bronchodilator agent; cardiotonic drug; diuretic; K-ATP channel agonist; sodium channel blocker; sympathomimetic agent; vasodilator agent |
glyburide | glyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group. Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide | monochlorobenzenes; N-sulfonylurea | anti-arrhythmia drug; EC 2.7.1.33 (pantothenate kinase) inhibitor; EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor; hypoglycemic agent |
troglitazone | Troglitazone: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity. | chromanes; thiazolidinone | anticoagulant; anticonvulsant; antineoplastic agent; antioxidant; EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; hypoglycemic agent; platelet aggregation inhibitor; vasodilator agent |
n-cyano-n'-(1,1-dimethylpropyl)-n''-(3-pyridinyl)guanidine | N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine: potassium channel opener | pyridines | |
repaglinide | piperidines | ||
cromakalim | Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352) | ||
rosiglitazone | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug | |
mk 767 | 5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide: an antihyperlipidemic agent that also functions as an insulin sensitizer, PPARalpha agonist, and PPARgamma agonist; structure in first source | ||
zeneca zd 6169 | Zeneca ZD 6169: an ATP-sensitive potassium channel opener; structure given in first source | ||
cromakalim | 1-benzopyran | ||
clamikalant | clamikalant: inhibits ATP-sensitive potassium channel; structure in first source | ||
zm226600 | ZM226600: an ATP-sensitive potassium channel opener; structure in first source | anilide | |
way 133537 | |||
ly 465608 | LY 465608: a nonthiazolidinedione agonist of both PPAR-alpha and PPAR-gamma of Ligand Pharm. and Eli Lilly | ||
bm 131246 | |||
nn 414 | NN 414: a hypoglycemic agent with insulin release modulating and potassium channel activating activities; structure in first source | ||
7-chloro-3-isopropylamino-4h-1,2,4-benzothiadiazine 1,1-dioxide | 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide: activates ATP-sensitive potassium channels; structure in first source |