Neurotransmitters and Neuromodulators (and a bit of Neuronal Communication) Flashcards
Define a neurotransmitter.
This refers to a substance that is released from the axon terminal of a presynaptic neuron on excitation, and which travels across the synaptic cleft to either excite or inhibit the target cell. [Many neurotransmitters are also hormones released into the bloodstream by endocrine cells in organs throughout the body.]
What criteria must be met by a substance for it to be considered a neurotransmitter (particularly classical transmitters)?
(a) It must be located in the presynaptic terminal in a bound or sequestered form.
(b) It should be released in response to stimulation (in sufficient quantities) to produce changes in postsynaptic potentials.
(c) There must be specific receptors for it on the post-synaptic membrane.
(d) Blocking the release prevents presynaptic activity from affecting postsynaptic activity.
Define a false neurotransmitter.
This is a biological amine that can be stored in presynaptic vesicles but that has little or no effect on postsynaptic receptors when released into the synaptic cleft.
What criteria of classical transmitters do gaseous and lipid transmitters not meet?
Synthesis of classical transmitters occurs in the presynaptic terminal. If you wanted to know if substance A is a classical transmitter what 2 things would you look for in the terminal and why would each tell you if substance A is likely synthesized or not?
- Look for precursor - this is what the transmitter is made from - the transmitter cannot be synthesized if this is not present.
- Look for enzymes capable of breaking down the precursor into the transmitter because you cannot convert the precursor without them.
List the synaptic transmitters under the following families:
a) Quaternary amines
b) Monoamines/biogenic amines: (in 1% of synapses)
(i) Catecholamines [derived from tyrosine]
(ii) Indoleamines [derived from tryptophan]
c) Amino acids (in 25-40% of synapses)
a) Acetylcholine (ACh) (5% of synapses)
b) (i) Norepinephrine, epinephrine, dopamine
(ii) serotonin, melatonin
c) Gamma-aminobutyric acid (GABA), glutamate (50% of synapses), glycine, histamine
Define a neuromodulator.
A neuromodulator is a neuroregulator that can act locally on other neurons or at a distance, increasing or decreasing the effect of neurotransmitters, but which does not itself initiate depolarisation.
Describe neuromodulation.
Neuromodulation is the physical process by which a given neuron uses one or more neurotransmitters to regulate diverse populations of neurons. This is in contrast to classical synaptic transmission, in which one presynaptic neuron directly influences a single postsynaptic partner. Neuromodulators secreted by a small group of neurons diffuse through large areas of the nervous system, affecting multiple neurons. Examples of neuromodulators include dopamine, serotonin, acetylcholine, histamine and others. [Neuromodulation can be conceptualized as a neurotrasmitter that is not reabsorbed by the presynaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the cerebrospinal fluid, influencing the activity of several other neurons in the brain. For this reason, some neurotransmitters are also considered to be neuromodulators, such as serotonin and acetylcholine.]
What are the major categories of neutrotransmitters and neuromodulators?
(1) Small-molecule transmitters include monoamines (e.g. acetylcholine, serotonin, histamine), catecholamines (dopamine, norepinephrine, and epinephrine), and amino acids (e.g. glutamate, GABA, glycine), biogenic amines, ATP and other purines.
(2) Large molecule transmitters include a large number of peptides called neuropeptides including substance P, enkephalin, vasopressin, and a host of others.
(3) Gaseous transmitters (nitric oxide, and carbon monoxide).
What are monoamines and how are they degraded?
These are neurotransmitters that contain a single amine group in their chemical structure and include norepinephrine, serotonin, and dopamine. Monoamines are degraded by intracellular (presynaptic) monoamine oxidase (MAO), and presynaptic catechol-O-methyl transferase (COMT).
Which neurotransmitters are classically considered excitatory?
acetylcholine, norepinephrine, epinephrine, dopamine, glutamate, serotonin
What neurotransmitters are classically considered inhibitory?
GABA, glycine
What determines if a neurotransmitter is excitatory or inhibitory?
The receptor
Distinguish between classic non-peptide neurotransmitters and peptide neurotransmitters.
Key: nonpeptide transmitters = NTs, peptide transmitters = PTs
⚚ NTs are synthesized and packaged in the nerve terminal, whereas PTs are synthesized and packaged in the cell body and are transported to the axon terminal by fast axonal transport. [site of synthesis]
⚚ NTs are synthesized in their active form, whereas with PTs, the active peptide is formed when it is cleaved from a much larger polypeptide that contains several neuropeptides. [zymogen?]
⚚ NTs are released into a synaptic cleft whereas PTs may be released some distance from the postsynaptic cell [there may be no well-defined synaptic structure]. [synaptic structure]
⚚ The action of NTs is terminated because of uptake into the presynaptic terminal via Na+-powered active transport, whereas the action of PTs is terminated by proteolysis or by the peptide diffusing away. [termination]
⚚ The action of NTs has a short latency, whereas that of PTs may have long latency and persist for many seconds. [duration of action]
⚚ NTs are usually present in small, clear vesicles wherease PTs are usually present in large, electron-dense vesicles. [vesicles]
Click on Answer to view extensive notes on the function, synthesis and degradation of acetylcholine.
In the peripheral nervous system, acetylcholine (ACh) is the transmitter at neuromuscular junctions, at sympathetic and parasympathetic ganglia, and of the postganglionic fibers from all parasympathetic ganglia and a few sympathetic ganglia. It is also a transmitter within the CNS, most prominently of neurons in some brainstem nuclei, in several parts of the basal forebrain (septal nuclei and nucleus basalis) and basal ganglia, and in the spinal cord (e.g., motor neuron axon collaterals).
Depending on the postsynaptic receptor, ACh can be either stimulatory (e.g., at the neuromuscular junction by motor neurons) or inhibitory (e.g., in parasympathetic postganglionic fibers to cardiac muscle). Cholinergic neurons from the basal forebrain areas project diffusely throughout the neocortex and to the hippocampus and amygdala, and they have been implicated in memory functions (ACh functions extensively in the brain to maintain cognitive function). Indeed, degeneration of these cells occurs in Alzheimer’s disease, a form of dementia in which memory function is gradually and progressively lost.
Acetylcholine is synthesized from acetyl coenzyme A and choline by the enzyme choline acetyltransferase, which is located in the cytoplasm of cholinergic presynaptic terminals. After synthesis, acetylcholine is concentrated in vesicles. After release, the action of acetylcholine is terminated by the enzyme acetylcholinesterase, which is highly concentrated in the synaptic cleft. Acetylcholinesterase hydrolyzes acetylcholine into acetate and choline. The choline is then taken up by an Na+ symporter in the presynaptic membrane for the resynthesis of acetylcholine.
