Neurotransmitters and Neuroactive Peptides

Contents of this Page Discovery Criteria Types Synthesis Transport Binding Inactivation

Communication of information betweenneurons is accomplished by movement of chemicals across a small gap calledthe synapse. Chemicals, called neurotransmitters are released from one neuron (thepresynaptic nerve terminal), then cross the synapse and areaccepted by the next neuron at a specialized site (the postsynapticreceptor). The action that follows activation of a receptor site may beeither depolarization (an excitatory postsynaptic potential) orhyperpolarization (an inhibitory postsynaptic potential).

Discovery ofNeurotransmitters Back in 1920, an Austrian scientist named Otto Loewi discoveredthe first neurotransmitter. Inhis experiment (which came to him in adream), he used two frog hearts. One heart (heart #1) was still connectedto the vagus nerve. Heart #1 was placed in a chamber that was filled withsaline. This chamber was connected to a second chamber that containedheart #2. So, fluid from chamber #1 was allowed to flow into chamber #2. Electrical stimulation of the vagus nerve (which was attached to heart #1) caused heart #1 to slow down. Loewi alsoobserved that after a delay, heart #2 also sloweddown. From this experiment, Loewi hypothesized that electricalstimulation of the vagus nerve released a chemical into the fluid ofchamber #1 that flowed into chamber #2. He called this chemical"Vagusstoff". We now know this chemical as the neurotransmitter calledacetylcholine. Otto Loewi's Experiment

NeurotransmitterCriteria Neuroscientists have set up a few guidelines or criteria to prove that achemical is really a neurotransmitter. Not all of the neurotransmittersthat you have heard about may actually meet every one of thesecriteria. The chemical must be produced within a neuron. The chemical must be found within a neuron. When a neuron is stimulated (depolarized), a neuron must releasethe chemical. When a chemical is released, it must act on a post-synapticreceptor and cause a biological effect. After a chemical is released, it must be inactivated. Inactivation can be through a reuptake mechanism or by an enzyme that stops the actionof the chemical. If the chemical is applied on the post-synaptic membrane, it shouldhave the same effect as when it is released by aneuron.

NeurotransmitterTypes There are many types of chemicals that act as neurotransmitter substances.Below is a list of some of them. Small Molecule Neurotransmitter Substances Acetylcholine (ACh) Dopamine (DA) Norepinephrine (NE) Serotonin (5-HT) Histamine Amino Acids Gamma-aminobutyric acid (GABA) Glycine Glutamate Aspartate Neuroactive Peptides - partial list!! bradykinin beta-endorphin bombesin calcitonin cholecystokinin enkephalin dynorphin insulin gastrin substance P neurotensin glucagon secretin somatostatin motilin vasopressin oxytocin prolactin thyrotropin angiotensin II sleep peptides galanin neuropeptide Y thyrotropin-releasing hormone gonadotropnin-releasing hormone growth hormone-releasing hormone luteinizing hormone vasoactive intestinal peptide

Synthesis ofNeurotransmitters

Acetylcholine is found in both the central andperipheral nervous systems. Choline is taken up by the neuron. When theenzyme called "choline acetyltransferase" is present, choline combines withacetyl coenzyme A (CoA) to produce acetylcholine.

Dopamine, norepinephrine and epinephrine are agroup of neurotransmitters called "catecholamines".Norepinephrine is also called "noradrenalin" and epinephrine isalso called "adrenalin". Each of these neurotransmitters is produced in astep-by-step fashion by a different enzyme.

Transport andRelease ofNeurotransmitters Neurotransmitters are made in the cell body of the neuron andthen transported down the axon to the axon terminal. Moleculesof neurotransmitters are stored in small "packages" calledvesicles (see the picture on the right).Neurotransmitters are released from the axon terminal when their vesicles"fuse" with the membrane of the axon terminal, spilling theneurotransmitter into the synaptic cleft.

ReceptorBinding Neurotransmitters will bind only to specific receptors on the postsynapticmembrane that recognize them.

Inactivation ofNeurotransmitters The actionof neurotransmitters can be stopped by three differentmechanisms
1. Diffusion: theneurotransmitter drifts away, out of the synaptic cleft where it can nolonger act on a receptor.	Diffusion
2. Enzymaticdegradation (deactivation): a specific enzyme changes the structureof the neurotransmitter so it is not recognized by the receptor. Forexample, acetylcholinesterase is the enzyme that breaks acetylcholine intocholine and acetate.	Enzymatic degradation
3. Reuptake: the whole neurotransmitter molecule is takenback into the axon terminal that released it. This is a common way theaction of norepinephrine, dopamine and serotonin is stopped...theseneurotransmitters are removed from the synaptic cleft so they cannot bindto receptors.	Reuptake

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