After studying this chapter, you should be able to:
List the major types of neurotransmitters.
Summarize the steps involved in the biosynthesis, release, action, and removal from the synaptic cleft of the major neurotransmitters.
Describe the various types of receptors for amino acids, acetylcholine, monoamines, neuropeptides, and opioids.
The dominant form of neuron-to-neuron or neuron-to-effector organ communication within the mammalian nervous system is mediated by the release of a chemical neurotransmitter that induces excitation or inhibition of the postsynaptic target. Neuromodulators are chemicals released by neurons that have little or no direct effects on their own but can modify the effects of neurotransmitters. This chapter provides a summary of the major properties of some of the most common chemical neurotransmitters, including excitatory and inhibitory amino acids, acetylcholine, catecholamines, and neuropeptides. For many of these chemicals, there are some common steps involved in the process of neurotransmission (Figure 7–1). These steps include uptake of a neurotransmitter precursor, biosynthesis of the neurotransmitter, its storage within synaptic vesicles, its release into the synaptic cleft in response to nerve impulses, binding of the neurotransmitter to receptors on the membrane of the postsynaptic target, and finally termination of its actions via diffusion away from the synapse, reuptake into the nerve terminal, or enzymatic degradation.
Biochemical events at a neuronal synapse. The drawing shows the common steps involved in neurotransmission. Step 1: Transport of a neurotransmitter precursor into a nerve terminal. Step 2: Synthesis of the neurotransmitter. Step 3: Transport of the neurotransmitter into a synaptic vesicle via a vesicle transporter. Step 4: An action potential induced influx of Ca2+, which leads to fusion of vesicles with the surface membrane and expulsion of the neurotransmitter and co-transmitters into the synaptic cleft. This step can involve synaptosome-associated proteins (SNAPs) and vesicle-associated membrane proteins (VAMPs). Step 5: The neurotransmitter acts on G-protein–coupled receptors or ionotropic receptors on the membrane of the postsynaptic target (a neuron, smooth muscle, skeletal muscle, or gland). Step 6: The action of the neurotransmitter is terminated by diffusion away from the synapse, reuptake into the nerve terminal, or enzymatic degradation. Specifics regarding each of these steps involved in transmission at cholinergic, adrenergic, and serotonergic synapses is detailed in the text.
Figure 7–2 shows the steps involved in the biosynthesis of some of the common neurotransmitters in the central nervous system (CNS) or peripheral nervous system. Table 7–1 summarizes properties of major neurotransmitters, including their receptors, second messengers, ion channel effects, and examples of receptor agonists and antagonists.
Biosynthesis of some common small-molecule neurotransmitters. (A) Glutamate is synthesized in the Krebs cycle by the conversion of α-ketoglutarate to the amino acid via the enzyme γ-aminobutyric acid transferase (GABA-T) or in nerve terminals by ...