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Neurotransmitters

Terms in this set (29)

Principles of Chemical Synaptic Transmission
- Basic Steps:
- Neurotransmitter synthesis
- Load neurotransmitter into synaptic vesicle
- Vesicles fuse to presynaptic terminal
- Neurotransmitter spills into synaptic cleft
- Binds to postsynaptic receptors
- Biochemical/Electrical response elicited in postsynaptic cell
- Removal of neurotransmitter from synaptic cleft
Major Classifications of Neurotransmitters
- Small molecule neurotransmitters (amino acids: glutamate, glycine, GABA, and amines: Dopamine, acetylcholine, Histamine)
- Large molecule neurotransmitters (Peptides are short amino acid chains (proteins) stored in and released from secretory granules: dynorphin, enkephalins)
- Centrally acting gasses (nitrous oxide, carbon monoxide)
- Neurotropic factors (nerve growth factor)
Neurotransmitter Synthesis and Storage
- Neurotransmitters are manufactured in two general ways
- Some are manufactured in the axon terminal from building blocks derived from food
- Transporter proteins in the cell membrane absorb the required precursor chemicals from the blood supply
- Sometimes these transporter proteins absorb the neurotransmitter itself ready-made
- Mitochondria in the axon terminal provides the energy needed to synthesize precursor chemicals into the neurotransmitter
- Other neurotransmitters are packaged in the cell body according to instructions contained in the neuron's DNA
- Molecules of these transmitters are packaged in membranes on the Golgi bodies and transported on microtubules to the axon terminal
- In the axon terminal, neurotransmitters manufactured in either way are wrapped in a membrane to form synaptic vesicles
- Some vesicles are stored in granules, others are attached to filaments in the terminal, and still others are attached to the presynaptic membrane, where they are ready for release into the synaptic cleft
- After a vesicle has been released from the presynaptic membrane, other vesicles move to the membrane location so that they, too, are ready for release when needed.
Neurotransmitter Release
- Mechanisms
- Process of exocytosis stimulated by the release of intracellular calcium
- Proteins alter conformation: activated
- Vesicle membrane incorporated into presynaptic membrane
- Neurotransmitter released
- Vesicle membrane recovered by endocytosis
Small Molecule Neurotransmitters
- Three Criteria
1) Synthesis and storage in presynaptic neuron
2) Released by presynaptic axon terminal
3) Produces response in postsynaptic cell
- Non-proteinaceous
- Molecular weight is less than 1000
- Are all released in a calcium-dependent fasion
- Act on receptors in a high-nanomolar or low micro-molar environment
- Are reused in their entirety or in part (acetylcholine)
- All are synthesized on endosomes by intracellular enzymes
- All act as a multiple receptor subtype
Neurotransmitter Synthesis
- Small molecule NTs are produced in specialized neurons that project or ascent via axons/pathways to other, typically higher areas of the brain, usually the cerebral cortex
- Acetylcholine (Ach)
- Nucleus Basalis of Meynert
- Septal nucleus
- Betz cells of the motor cortex
Neurotransmitter Chemistry
- Cholinergic (ACh) neurons
Neurotransmitter Synthesis II
- Dopamine (substantia nigra)
- Norepinephrine (Locus cerebellum)
- Epinephrine (Secreted by the adrenal medulla)
- Serotonin (Raphe nuclei)
- Histamine (hypothalamus)
Catecholamines
- Catecholaminergic Neurons
- Involved in movement, mood, attention and visceral function
- Tyrosine: Precursor for three neurotransmitters that contain catechol group (Dopamine, Norepinephrine, and epinephrine)
Catecholaminergic NTs
- All contain the enzyme tyrosine hydroxylase (TH) which converts tyrosine to dopa
- Dopa is converted into dopamine by dopa decarboxylase (abundant in all catecholaminergic neurons)
- Neurons that use NE also contain dopamine B-hydroxylase (DBH), which converts DA to NE
- Adrenergic neurons (epinephrine) contain the enzyme phentolamine methyltransferase (PNMT), which converts NE to epinephrine
- Two step process: NE synthesized in vesicles, released into the cytosol for conversion; epinephrine must again be transported into vesicles to be released
- Action is terminated by selective reuptake into the axon terminal by NA+-dependent transporters. Once inside, catecholamines may be reloaded into vesicles or destroyed by MAO
Monoamine: Serotonin
- Serotonergic Neurons
- Amine neurotransmitter (serotonin 5-HT derived from tryptophan)
- Regulates mood, emotional behavior, sleep
- Synthesis of serotonin (tryptophan hydroxylase: converts tryptophan into 5-HTP; 5HTP decarboxylase: converts 5-HTP to 5-HT
Amino Acids
- Amino acidergic neurons
- Amino acid neurotransmitters: Glutamate, glycine, gamma-an=minobutyric acid (GABA),
- Differences among amino acidergic neurons is quantitative, not qualitative
- Glutamate acid decarboxylase (GAD): key enzyme in GABA synthesis, good marker for GABAergic neurons, GABAergic neurons are major of synaptic inhibition in the CNS
- Glutamate synthesis is the exception to the rule
- Synthesized by a number of chemical reactions, including the breakdown of glucose, by enzymes that exist in all neural cells, and form glutamine
-Glutamate is taken up by astrocytes and stored
- GABA is synthesized directly from glutamate
Other neurotransmitter candidates and intercellular messengers
- ATP: excites neurons, binds to purinergic receptors
- Endocannabinoids
- Retrograde messengers
Neurotransmitter Degradation and Recovery
- Diffusion: Moves away from the space
- Reuptake: NT re-enters the presynaptic axon terminal
- Enzymatic: destruction inside terminal cytosol or the synaptic cleft
- Desensitization: ex: AChE cleaves Ach into inactive state
Degredation, Reuptake, and Converstion of NTs
- ACh: By acetylcholinesterase (AChE), into choline and acetic acid. AChE is secreted into the synapse by both cholinergic and non-cholinergic neurons
- 5-HT: Removed from the synaptic cleft by a specific transporter protein (reuptake). In cytosol of serotonergic axon terminal, 5-HT is either reloaded into vesicles or degraded by the enzyme monoamine oxidase (MAO)
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