The following is some straightforward information about the most common neurotransmitters. Also, be sure to read the blurbs under "Disorders and Terminology" on the handout.
Acetylcholine is the neurotransmitter released by two types of neurons you hear about frequently in physiology: parasympathetic postganglionic neurons and somatic efferent neurons. In the parasympathetic case, the receptor is a seven transmembrane domain receptor coupled to a trimeric G protein. In the somatic efferent case, the receptor on the skeletal muscles cells is a ligand gated ion channel that produces fast excitatory postsynaptic potentials.
Refer to the handout for descriptions of neuromuscular blocking agents and cholinesterase inhibitors.
Glutamate is the most abundant excitatory neurotransmitter in the brain and spinal cord. It is released, for example, by afferent neurons. In many cases, the receptor is a ligand gated ion channel that produces fast postsynaptic potentials. But recall the NMDA receptor from the previous webpage and from our discussion of stroke. NMDA antagonists are used sometimes for chronic pain.
Usually known by its initials, GABA is the most abundant inhibitory neurotransmitter in the brain. Benzodiazepines, such as diazepam (Valium) bind to a separate site on the GABA receptor and increase the effectiveness of GABA. In this way, these widely used substances increase the level of inhibition widely throughout the brain, making them useful as sedatives, muscle relaxants, anticonvulsants and anesthetics.
The catecholamines are dopamine, norepinephrine, and epinephrine. Their synthesis begins with the amino acid tyrosine, which is converted to L-dopa (which you will hear about after the midterm), which is then coverted to dopamine. A further enzyme can convert this to norepinephrine and a further to epinephrine.
The receptors are all seven transmembrane domain proteins linked to trimeric G proteins.
You already know about the role norepinephrine plays as the neurotransmitter released from sympathetic postganglionic neurons and the role of epinephrine as a hormone. Their receptors are termed adrenergic receptors, which are of two types, alpha and beta.
Many important drugs, of course, block or stimulate adrenergic receptors in order to suppress or accentuate sympathetic effects. Dopamine is sometimes used as systemic drug because it also activates adrenergic receptors. But dopamine injected into the blood does not cross the blood brain barrier.
Dopamine and norepinephrine play major roles in the brain, with widely branching axons that go to many areas. Dopamine plays roles in areas such as motivation, mood and learning. Norepinephrine is especially important in controlling the level of excitation or alertness of the spinal cord and brain.
Phenothiazines such as chlorpromazine (Thorazine) block dopamine receptors (among other actions) and are used as anti-psychotic drugs. Since the introduction of chlorpromazine in the 1960's, there has been a great decrease in the number of institutionalized patients.
Various drugs are used to block the reuptake of dopamine and norepinephrine, thereby increasing their time of action in the synaptic cleft. The tricyclic antidepressants block the reuptake of dopamine, norepinephrine and serotonin (see below). They are used for neuropathic pain and sometimes for depression and certain psychiatric disorders.
Serotonin is also derived from an amino acid, also acts on a seven transmembrane domain receptor, and also is released from neurons with widely branching axons. The best illustration of its role in the brain is the widespread use of selective serotonin reuptake inhibitors as anti-depressants. Fluoxetine (Prozac) is one example.
Neuropeptides are an important class of neurotransmitters, but their packaging in vesicles and their receptors are quite different than the above neurotransmitters. Neuropeptides are cleaved from proteins synthesized in the rough endoplasmic reticulum. Typically, a small molecular weight neurotransmitter is added to the vesicle with the neuropeptide in the presynaptic terminal.
One example discussed on the Pain webpage is the peptide substance P, which is released along with glutamate from C pain afferent neurons. Another important class of neuropeptides discussed on that page are enkephalins, which reduce the flow of pain information.
For general interest, let me list a few other neurotransmitters, although we aren't actually covering them at this time: adenosine, which blocks caffiene, nitric oxide, the weird, diffusible gas and histamine, which has a role, for example, in sleep and wakefullness.