They are synthesized in the presynaptic neuron from precursors and then packaged in synaptic vesicles , and released after reaching of an action potential to the presynaptic neuron , usually by Exocytosis.
After releasing of a neurotransmitter into the synaptic cleft , it binds to a receptor on the post-synaptic membrane and then causes a response in the postsynaptic target cell.
Electrical signal ( action potential) is necessary for releasing of a neurotransmitter.
* criteria used to determine a neurotransmitter :
Classical criteria were used to determine a given chemical as neurotransmitter , some of them are:
1- To exist in the presynaptic neuron in sufficient quantity
2- To be produced in the presynaptic neuron ( to have precursors and enzyme system that
3- to be present within a neuron
3- to have specific postsynaptic receptors and to have an effect on the postsynaptic membrane after binding to its receptor.
4- To be inactivated later , either by special inactivating enzymes or by reuptake.
* Discovery of neurotransmitter:
Acetylcholin was the first neurotransmitter to be discovered in 1921 by Otto Lowei. ( read about the discovery of acetylcholin to enrich your knowledge in the history of medicine). Later in 1946 Norepinephrine was discovered , as Dopamine was discovered in 1950 . Many neurotyransmitters were discovered after that till now.
* Classification of neurotransmitters :
Neurotransmitters could be classified regarding their chemical structure or their effect on the postsynaptic target cells :
Structural classification of neurotransmitter :
1- Monoamine neurotransmitters : such as epinephrine , Norepinephrine , Dopamine , Histamine , and Serotonin.
2- Amino acids : such as glutamate , GABA m Glycine , and asparate.
3- Peptides : such as enkephalin , endorphin , substance P , Bradykinin ...etc.
4- Others : some ions like Zinc could act as neurotransmitters , and some gases like NO , Co and H2N could also act as neurotransmitters.
Functional classification of neurotransmitters : Depending on their effect on postsynaptic membrane , neurotransmitter could be classified as : Excitatory ( such as glutamate) or inhibitory ( such as GABA) neurotransmitters. This depends on the effect of neurotransmitter on the postsynaptic receptor , which either cause : excitatory postsynaptic action potential ( EPSP) or inhibitory postsynaptic potential ( IPSP) . Both types of potentials could also be classified as rapid EPSP or IPSP , or slow EPSP or IPSP depending on transducing mechanism : ion channels for the rapid and second messenger for the slow.
Remember: It is an oversimplification to classify neurotransmitters into excitatory and inhibitory , because some of the inhibitory neurotransmitters , like GABA acts as an excitatory neurotransmitter during early brain development , while some neurotransmitters like acetylcholin has both excitatory and inhibitory neurotransmitters , and some receptors of neurotransmitters produce an effect that can not be classified as excitatory or inhibitory.
* Fate of neurotransmitters : After releasing of a neurotransmitter it may have one of the following fates:
1- Consuming: it may be used up and broken down .
2- Degradation : By enzymes .
3- Reutilization : by reuptake mechanism.This is the most common fate.
* Types of inhibitory effects of neurotransmitter :
1- direct inhibition : When the neurotransmitter causes hyperpolarization of postsynaptic membrane ( e.g : GABA causes influx of chloride ions inside the postsynaptic membrane , which in turn hyperpolarize it. other example : Curare binds to the receptors of acetylcholine on the postsynaptic membrane and cause and prevent Ach from acting on those receptors).
2- Indirect inhibition: when a neurotransmitter is impaired to be released from the presynaptic membrane ( e.g botulinum toxin binds to presynaptic membrane and inhibits the release of acetylcholine . other examples : in some diseases like Lumert- Eaton syndrom : antibodies destruct calcium channels in the presynaptic neuron and interfere with releasing of the neurotransmitter )