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Neurotransmitters are chemical signals that neurons use to communicate with other neurons and different cells. Most have other uses in the body as well.
Unlike the neuromuscular junction, neuron synapses have more subtle and complex characteristics. Neurotransmitters can stimulate, inhibit, or modulate the postsynaptic neuron.
Acetylcholine (ACh) is a common neurotransmitter secreted by a variety of neurons.
It binds to two different receptors - Ionotropic (fast) nicotinic receptors and metabotropic (slow) muscarinic receptors.
Acetylcholine is restricted in the CNS, being limited to:
ACh is made in the pre-synaptic terminal by choline acetyltransferase and is stored and released from vesicles, each which contains 6000-10,000 ACh molecules.
ACh is primaily removed form the synapse by the action of acetylcholineesterase (AChE)
anticholinergic effects can cause dry mouth, constipation, blurry vision, delerium, cognitive impairment, etc
Dopamine is a neurotransmitter important for lots of things. It is also used as a drug.
Dopamine is an important neurotransmitter in the CNS. It is involved in the following systems:
D2 blockers can
70-80% of CNS neurons use GABA as a neurotransmitter; as such, the brain is largely inhibitory
GABAA are ionotropic
GABAB are metabotropic, linked via G proteins to opening K channels or suppressing Ca channels
benzodiazepines and barbiturates each bind to an allosteric site on GABAA channels, facilitating Cl- influx
Glutamate, an amino acid, is the most common excitatory neurotransmitter in the nervous system.
Glutamine is converted to glutamate by glutaminase in the presynaptic cell, stored, and released.
Glutamate can act on four major classes of receptors.
AMPA receptors are ionotropic and are found in most excitatory synapses in the brain. They let Na+, K+, and very little Ca2+.
NMDA receptors, of which there are many, are also ionotropic. During hyperpolarization, NMDA receptors are blocked by magnesium, only opening above - 60 mV. This makes NMDA channels both ligand gated and voltage gated. They co-exist with AMPA-gated channels, opening more slowly once other channels have opened.
kainate receptor channels are a mystery.
mGlu Receptors are metabotropic.
Surrounding glial cells take up glutamate from the synapse, convert in back to glutamine, and return it to pre-synaptic cells.
Most common excitatory NT
amino acid
every neuron has glutamate receptors
Glutamine is converted to glutamate by glutaminase in the presynaptic cell, stored, and released.
Receptors include AMPA-R, NMDA-R, and MGluR.
NMDA receptors are blocked by magnesium during cell hyperpolarization, and allow Ca influx when the cell is depolarized.
these are thought to underly learning and memory and cell death during stroke.
Surrounding glial cells take up glutamate from the synapse, convert in back to glutamine, and return it to pre-synaptic cells.
Norepinephrine (NE) is the primary neurotransmitter of the sympathetic nervous system. Its effects are very similar to those of the hormone epinephrine, released by the adrenal medulla.
NE is used by modulatory system neurons in the locus coeruleus in the reticular activating system to affect arousal, anxiety, etc.
Norepinephrine (NE) is released by most postganglionic cells of the SNS, where it binds to a variety of receptors.
Receptor Locations | Physiological Effects | Intracellular effects | Agonist | Antagonist | |
---|---|---|---|---|---|
α1 | smooth muscle cells | peripheral vasoconstriction | increases IP3, DAG, and calcium | phenylephrine | prazosin |
α2 | presynaptic adrenergic nerve terminals, platelets, lipocytes, SMCs | negative feedback on NE secretion; platelet aggregation | inhibits adenylate cyclase, decreasing cAMP | clonidine | Yohimbine |
β1 | cardiomyocytes, kidney | stimulates adenylate cyclase, increasing cAMP levels | isoproterenol, dobutamine | atenolol, metoprolol | |
β2 | lung, intestine | bronciodilation dec. intestinal motility |
albuterol, salbutamol | ||
β3 |
Serotonin (5-HT) is a vasoactive amine that acts both as a neurotransmitter and a local signal in inflammation. It has major effects on the brain, as well as the gastrointestinal system.
Serotonin acts as both an excitatory or inhibitory neurotransmitter within the brain, with diffuse connections. Signaling appear to mediate sleep-wake cycles and different stages of sleep, as well as control of mood and emotional behaviour.
Cell bodies are located primarily in the raphe nuclei, found in the brainstem's midbrain and medulla (and pons?).
Serotonin is produced, stored, and released by platelets following aggregation or stimulation by platelet activating factor. It has inflammatory effects similar to histamine, causing arteriole dilation and increasing venule permeability.
Serotonin is also produced by enterochromaffin cells in the pancreas.
Serotonin is produced from the amino acid tryptophan and released into the intrasynaptic space upon axonal stimulation. There are various receptor families.
Serotonin is taken back into the presynaptic cell, where it is metabolized by monoamine oxidase.
Different serotonin receptors are as follows:
Receptor |
Action |
5-HT 1A |
neuronal inhibition; regulation of sleep, feeding, thermoregulation increased stimulation: anxiety; decreased stimulation: depression |
5-HT 1D |
locomotion, muscle tone |
5-HT 2A |
neuronal excitation; learning, vasoconstriction, platelet aggregation |
5-HT 2B |
stomach contraction |
5-HT 3 |
nausea, vomiting, anxiety |
5-HT 4 |
gastrointestinal motility |
Many hallucinogenic drugs, such as LSD, appear to interact with serotonergic systems.
Disorders of serotonin appear to be involved in a number of psychiatric and other conditions, including:
The four main criteria used to define neurotransmitters are:
There are two main fashions of transporting neurotransmitters down the axon.
Slow axonal transport occurs via synthesis in the cell body, are packaged in the golgi, and are then transported down the axon.
Fast transport...
In general, decarboxylation activates compunds, while deamination inactivates them.