For the most part, neurons in the human brain communicate with one another by releasing chemical messengers called neurotransmitters. A large number of neurotransmitters are now known and more remain to be discovered. Neurotransmitters evoke postsynaptic electrical responses by binding to members of a diverse group of proteins called neurotransmitter receptors. There aretwo major classes of receptors: those in which the receptor molecule is also an ion channel, and those in which the receptor and ion channel are separate molecules. The former are called ionotropic receptors or ligandgated ion channels, and give rise to fast postsynaptic responses that typically last only a few milliseconds. The latter are called metabotropic receptors, and they produce slowerpostsynaptic effects that may endure much longer. Abnormalities in the function of neurotransmitter systems contribute to a wide range of neurological and psychiatric disorders. As a result, many neuropharmacological therapies are based on drugs that affect neurotransmitter release, binding, and/or removal.
Neurotransmitters and Their Receptors
Categories of Neurotransmitters
More than 100different agents are known to serve as neurotransmitters. This large number of transmitters allows for tremendous diversity in chemical signaling between neurons. It is useful to separate this panoply of transmitters into two broad categories based simply on size (Figure 6.1). Neuropeptides are relatively large transmitter molecules composed of 3 to 36 amino acids. Individual amino acids, such asglutamate and GABA, as well as the transmitters acetylcholine, serotonin, and histamine, are much smaller than neuropeptides and have therefore come to be called small-molecule neurotransmitters. Within the category of small-molecule neurotransmitters, the biogenic amines (dopamine, norepinephrine, epinephrine, serotonin, and histamine) are often discussed separately because of their similar chemicalproperties and postsynaptic actions. The particulars of synthesis, packaging, release, and removal differ for each neurotransmitter (Table 6.1). This chapter will describe some of the main features of these transmitters and their postsynaptic receptors.
As mentioned in the previous chapter, acetylcholine (ACh) was the first substance identified as a neurotransmitter. In additionto the action of ACh as the neurotransmitter at skeletal neuromuscular junctions (see Chapter 5), as well as the neuromuscular synapse between the vagus nerve and cardiac
130 Chapter Six
SMALL-MOLECULE NEUROTRANSMITTERS O Acetylcholine (CH3)3N AMINO ACIDS Glutamate H3N
BIOGENIC AMINES CH3 CATECHOLAMINES Dopamine CH2 HO OH CH2 NH3
H C CH2 CH2COO−
COOH Aspartate H3N
OH Norepinephrine HO OH CH2 CH2 NH3
H C CH2
OH GABA H3N
H C H
OH COO− INDOLEAMINE Serotonin (5-HT) HO CH2 N CH2 NH3
PURINES ATP O O− P O− O O P O− O O P O− H H OH OH O CH2 O N N
NH2 N IMIDAZOLEAMINE N Histamine HN N
PEPTIDE NEUROTRANSMITTERS (more than 100 peptides, usually 3−30 amino acids long) Example: Methionine enkephalin (Tyr–Gly–Gly–Phe–Met) O H3N
O H N H C H C H N H C H
O C H N H C CH2
O C H N H C CH2 CH2 S
O C O−
H C CH2
OH Tyr Gly Gly Phe
Neurotransmitters and Their Receptors 131
Figure 6.1 Examples of small-molecule and peptideneurotransmitters. Small-molecule transmitters can be subdivided into acetylcholine, the amino acids, purines, and biogenic amines. The catcholamines, so named because they all share the catechol moiety (i.e., a hydroxylated benzene ring), make up a distinctive subgroup within the biogenic amines. Serotonin and histamine contain an indole ring and an imidazole ring, respectively. Size differences...
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