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OBJECTIVES

Objectives

After studying this chapter, the student should be able to:

  • Diagram the synthesis, packaging, and transport of the monoamine neurotransmitters (NTs) dopamine, norepinephrine (NE), epinephrine (EP), serotonin, and histamine.

  • Identify the localization of monoaminergic neuron cell bodies in the brainstem or hypothalamus and their projections in the brain and spinal cord.

  • Describe the functions of the monoamine NTs.

  • Distinguish the types of purine NTs and their metabolism, receptors, and functions.

  • Illustrate the synthesis, packaging, and removal of neuropeptides (NPs).

  • Identify the main categories of NPs and outline their general functions.

  • Define unconventional NTs, gasotransmitters, and endocannabinoids.

  • Diagram the synthesis and targets of unconventional NTs.

MONOAMINES

Monoamine neurotransmitters (NTs) are a subgroup of biogenic amines that contain an amino and aromatic group and function as NTs. The 3 categories of monoamine NTs are the catecholamines, which include dopamine (DA), norepinephrine (NE), and epinephrine (EP); the indolamine serotonin (abbreviated by its chemical name 5-hydroxytryptamine [5-HT]); and the imidazolamine histamine (HA) (Figure 9–1). Monoamine neuron cell bodies are located in the brainstem or hypothalamus, with their axons projecting throughout the brain and spinal cord. Although they represent only a small percentage of the total number of neurons in the brain, monoaminergic neurons function in important processes, including emotion, arousal, mood, reward, sleep, and memory. Therapeutic drugs that modulate monoamine transmission are used to treat depression, bipolar disorder, attention deficit hyperactivity disorder (ADHD), anxiety disorders, posttraumatic stress disorder (PTSD), schizophrenia, and Parkinson disease (PD). Several addictive drugs of abuse, including cocaine and methamphetamine, lead to alteration of neuronal circuits involving monoamines. In the peripheral nervous system (PNS), monoamines are synthesized and released by postganglionic sympathetic neurons, adrenal chromaffin cells, and neurons in the gastrointestinal (GI) tract. All monoamines function via specific metabotropic G-protein–coupled receptors (GPCRs); 5-HT also employs an ionotropic receptor (Figure 9–2). Given their mechanisms of action through G proteins and second messenger pathways, monoamines function in slow synaptic transmission and neuromodulation.

FIGURE 9–1

Schematic of a presynaptic monoaminergic neuron. All monoamines are transported into synaptic vesicles by a vesicular monoamine transporter (VMAT1 or VMAT2). Following release into the synaptic cleft, monoamines are transported back into the presynaptic neuron or nearby astrocytes by the selective transporters for dopamine (DAT), norepinephrine (NET) or serotonin (SERT).

FIGURE 9–2

Monoamines function through metabotropic G-protein–coupled receptors. A. Under basal conditions, the α subunit is bound to GDP and the G protein exists in a heterotrimer complex composed of a single α, β, and γ subunit. B. After the receptor (R) is activated by its ligand (e.g., a monoamine), R associates with the α subunit, causing the α subunit to release the bound GDP. Subsequently GTP (present in higher concentrations than GDP) binds to the α subunit. C. GTP binding causes the dissociation of the α subunit from its βγ subunits ...

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