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OBJECTIVES

OBJECTIVES

After studying this chapter, you should be able to:

  • List the major types of neurotransmitters and neuromodulators that are broadly characterized as small-molecule transmitters, large-molecule transmitters, and gas transmitters.

  • Summarize the five common steps involved in the biosynthesis, release, action, and removal from the synaptic cleft of the major small-molecule and large-molecule neurotransmitters.

  • Compare the actions initiated by binding of a neurotransmitter to an ionotropic (ligand-gated) versus metabotropic (G-protein-coupled, GPCR) receptor and identify the second messengers involved in mediating the actions of neurotransmitters that act on GPCRs.

  • Recognize the major distribution of the various types of receptors that mediate the functional responses of the common neurotransmitters: amino acids (glutamate and GABA), acetylcholine, monoamines (norepinephrine, epinephrine, dopamine, and serotonin), and opioid peptides.

  • List receptor antagonists for each of the common neurotransmitters.

  • Describe the role of nitric oxide and carbon monoxide (CO) in modulating synaptic transmission.

  • Provide examples of how neurotransmitter dysfunction contributes to some neuropathological disorders.

INTRODUCTION

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, monoamines, and neuropeptides. For many of these chemicals, there are some common steps involved in the process of neurotransmission. These steps include uptake of a neurotransmitter precursor into a nerve terminal, biosynthesis of the neurotransmitter, its storage within synaptic vesicles, its release into the synaptic cleft in response to the arrival of a wave of depolarization into the presynaptic nerve terminal, 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.

CHEMISTRY OF TRANSMITTERS

Many neurotransmitters and the enzymes involved in their synthesis and catabolism are localized in nerve endings. There are three main classes of chemical substances that serve as neurotransmitters and neuromodulators: small-molecule transmitters, large-molecule transmitters, and gas transmitters. Small-molecule transmitters include amino acids (eg, glutamate, γ-aminobutyric acid [GABA], and glycine), acetylcholine, and monoamines (eg, norepinephrine, epinephrine, dopamine, and serotonin). Large-molecule transmitters include neuropeptides such as substance P, enkephalin, and vasopressin. Neuropeptides are often co-localized with one of the small-molecule neurotransmitters (Table 7–1). Gas transmitters include nitric oxide (NO) and carbon monoxide (CO).

TABLE 7–1Examples of co-localization of small-molecule transmitters with neuropeptides.

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