Page last updated: 2024-10-24

aminergic neurotransmitter loading into synaptic vesicle

Definition

Target type: biologicalprocess

The active transport of aminergic neurotransmitters into a synaptic vesicle. This import is fuelled by an electrochemical gradient across the vesicle membrane, established by the action proton pumps. [GOC:ai]

The process of aminergic neurotransmitter loading into synaptic vesicles is a complex and tightly regulated process that ensures the efficient release of these signaling molecules at the synapse. Here's a detailed breakdown:

1. **Synthesis:** Aminergic neurotransmitters like dopamine, norepinephrine, and serotonin are synthesized in the presynaptic neuron's cytoplasm. This synthesis involves a series of enzymatic steps using precursor molecules. For example, dopamine is synthesized from L-tyrosine through the action of tyrosine hydroxylase and dopa decarboxylase.

2. **Transport into Vesicles:** Once synthesized, the neurotransmitters must be packaged into synaptic vesicles for storage and release. This process is mediated by a specialized protein called the **vesicular monoamine transporter (VMAT).** VMAT is a transmembrane protein that utilizes the electrochemical gradient generated by proton pumps to move neurotransmitters into the vesicle lumen. This transport is highly specific for each type of aminergic neurotransmitter, ensuring the correct loading of the appropriate neurotransmitter into the vesicle.

3. **Proton Gradient:** The energy for VMAT's transport comes from the proton gradient established by **vesicular proton ATPases (V-ATPases).** These ATPases use the energy from ATP hydrolysis to pump protons into the vesicle lumen, creating an electrochemical gradient. This gradient drives the movement of neurotransmitters into the vesicle against their concentration gradient.

4. **Regulation:** The process of neurotransmitter loading is tightly regulated to ensure proper synaptic function. Several factors influence this process:
* **Availability of Precursors:** The availability of precursor molecules for neurotransmitter synthesis directly influences the amount of neurotransmitter that can be packaged into vesicles.
* **VMAT Expression Levels:** The expression levels of VMAT can be regulated, affecting the rate of neurotransmitter uptake into vesicles.
* **Cellular Calcium Levels:** Calcium plays a critical role in neurotransmitter release. Increased calcium levels can stimulate VMAT activity and enhance neurotransmitter loading.
* **Pharmacological Agents:** Certain drugs can influence VMAT activity, affecting the amount of neurotransmitter packaged into vesicles. For example, reserpine, a drug used to treat hypertension, inhibits VMAT, reducing neurotransmitter levels in the synapse.

5. **Vesicle Release:** Once loaded with neurotransmitters, synaptic vesicles are primed for release. Upon arrival of an action potential at the presynaptic terminal, calcium influx triggers the fusion of vesicles with the presynaptic membrane, releasing the neurotransmitters into the synaptic cleft.

6. **Recycling:** After release, synaptic vesicles are recycled through a process called **endocytosis**. Empty vesicles are retrieved from the plasma membrane and re-enter the presynaptic cytoplasm where they are re-loaded with neurotransmitters.

This complex process of aminergic neurotransmitter loading into synaptic vesicles is essential for ensuring proper synaptic transmission and neuronal communication. It is a dynamic and regulated process that is influenced by multiple factors, ensuring the efficient and precise delivery of these important signaling molecules.'
"

Proteins (3)

ProteinDefinitionTaxonomy
Chromaffin granule amine transporterA chromaffin granule amine transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:P54219]Homo sapiens (human)
Synaptic vesicular amine transporterA synaptic vesicular amine transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05940]Homo sapiens (human)
Tyrosine 3-monooxygenaseA tyrosine 3-monooxygenase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P07101]Homo sapiens (human)

Compounds (12)

CompoundDefinitionClassesRoles
ketanserinketanserin : A member of the class of quinazolines that is quinazoline-2,4(1H,3H)-dione which is substituted at position 3 by a 2-[4-(p-fluorobenzoyl)piperidin-1-yl]ethyl group.

Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
aromatic ketone;
organofluorine compound;
piperidines;
quinazolines
alpha-adrenergic antagonist;
antihypertensive agent;
cardiovascular drug;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
serotonergic antagonist
reserpinereserpine : An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.

Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.
alkaloid ester;
methyl ester;
yohimban alkaloid
adrenergic uptake inhibitor;
antihypertensive agent;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
environmental contaminant;
first generation antipsychotic;
plant metabolite;
xenobiotic
tetrabenazine9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one : A benzoquinolizine that is 1,2,3,4,4a,9,10,10a-octahydrophenanthrene in which the carbon at position 10a is replaced by a nitrogen and which is substituted by an isobutyl group at position 2, an oxo group at position 3, and methoxy groups at positions 6 and 7.benzoquinolizine;
cyclic ketone;
tertiary amino compound
2h-benzo(a)quinolizin-2-ol, 2-ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-: Proposed catecholamine depletor.
lobeline(-)-lobeline : An optically active piperidine alkaloid having a 2-oxo-2-phenylethyl substituent at the 2-position and a 2-hydroxy-2-phenylethyl group at the 6-position.aromatic ketone;
piperidine alkaloid;
tertiary amine
nicotinic acetylcholine receptor agonist
dihydrotetrabenazinedihydrotetrabenazine: RN given refers to cpd without isomeric designationisoquinolines
n-n-propylnorapomorphineaporphine alkaloid
monoiodotyrosine3-iodo-L-tyrosine : The monoiodotyrosine that is L-tyrosine carrying an iodo-substituent at position C-3 of the benzyl group.

iodotyrosine : A tyrosine derivative which has at least one iodo-substituent on the benzyl moiety.

monoiodotyrosine : An iodotyrosine carrying a single iodo substituent.

Monoiodotyrosine: A product from the iodination of tyrosine. In the biosynthesis of thyroid hormones (THYROXINE and TRIIODOTHYRONINE), tyrosine is first iodized to monoiodotyrosine.
amino acid zwitterion;
L-tyrosine derivative;
monoiodotyrosine;
non-proteinogenic L-alpha-amino acid
EC 1.14.16.2 (tyrosine 3-monooxygenase) inhibitor;
human metabolite;
mouse metabolite
lobeline
11-hydroxy-n-(n-propyl)noraporphine hydrochloride, (r)-isomer
lobelanelobelane: structure in first source
mrk 560MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source