Neurotransmitters
Fall 2002

Neuropharmacology is the study of chemicals that affect the nervous system.

Chemical messengers can be classified into 3 types:

1) Neurotransmitters--carry messages across a synapse.
2) Neuromodulators--modulate the activity of neurons over a short distance.
3) Hormones--released by glands into the blood to travel throughout the body.

This lecture will focus on neurotransmitters (more on hormones when we get to lectures on stress and sex).
 

 There are thousands of chemicals in the body. These chemicals range from simple molecules to relatively large proteins.
The 4 common criteria used to distinguish a neurotransmitter from chemical garbage are (Figure 6.1).
1) Synthesis--Neuron has to be able to make the transmitter. For example, neurons uses enzymes (another protein) to convert AAs into neurotransmitters.

2) Storage--Neurotransmitters are located in presynaptic terminals (i.e., stored in vesicles). Anatomists use antibodies to label transmitters (Figure 6.2).

3) Release--Action potentials in presynaptic neurons cause neurotransmitters to be released. The released transmitter should affect the postsynaptic target.

4) Removal--There must be a mechanism to remove the neurotransmitter from the synaptic cleft. The two most common mechanisms are:

a) Reuptake--recycle the neurotransmitter into the presynaptic element.
b) Enzymatic degradation--inactivate the transmitter by changing itís chemical structure. The following substances appear to meet these criteria for a neurotransmitter. Acetylcholine (ACh)--the enzyme choline acetlytransferase makes ACh by combining Acetyl CoA + Choline (Figure 6.10). ACh is involved in muscle contractions, heart rate, and other behaviors
 

Monoamines: The following three neurotransmitters are monoamines.
 

a. Serotonin (5-HT)--enzymes convert the amino acid tryptophan into 5-hydrozytraptamine (5-HT) (Figure 6.13). 5-HT is located in the raphe nuclei and appears to be involved in regulating mood as indicated by the effects of Prozac and Ecstasy which increase 5-HT levels.

b. Dopamine (DA)--enzymes convert the amino acid tyrosine into DOPA and then into DA (Figure 6.12). DA is located in the Substantia nigra and appears to be invoved in reward and initiating movement.

c. Norepinephrine (NE )--an enzyme converts DA into NE (Figure 6.12). NE is located in the Locus Coreuleus and appears to contribute to many behaviors (heart rate, mood, etc.). Because DA & NE both contain a catechol ring, they are also classified as Catecholamines (Figure 6.11)
 
 

 Amino Acids make up another class of neurotransmitters (Figure 6.14).
  a. Glutamate--This neurotransmitter is an amino acid that occurs naturally in food. It appears that nearly every neuron in the brain responds to glutamate by producing an EPSP. Glutamate probably contributes to all behavior.

b. GABA (gamma-amino butyric acid)--the enzyme glutamic acid decarboxylase converts glutamate into GABA in many neurons (Figure 6.15). GABA binding to a receptor appears to cause an IPSPs in nearly every neuron. The loss of GABAergic neurons will result in seizures because neurons are not inhibited. Common drugs like benzodiazepines and barbiturates facilitate GABA by binding to GABA receptors (Figure 6.20).
 
 

 Peptides are a sequence of amino acids that can act as a neurotransmitter. Some examples include: Enkephalin (5 amino acids)--involved in blocking pain
Substance P (11 AAs)--is released by pain fibers Neuroransmitters produce EPSPs or IPSPs when they bind to a receptor. Although neurons appear to be fairly consistent, an EPSP or IPSP depends on the receptor, not the neurotransmitter, because the receptor determines which channel is opened or which second messenger is activated.
 

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