146 SECTION IIPhysiology of Nerve & Muscle Cells
Other Substances
Prostaglandins are derivatives of arachidonic acid found in
the nervous system. They are present in nerve-ending frac-
tions of brain homogenates and are released from neural tis-
sue in vitro. A putative prostaglandin transporter with 12
membrane-spanning domains has been described. However,
prostaglandins appear to exert their effects by modulating re-
actions mediated by cAMP rather than by functioning as syn-
aptic transmitters.
Many steroids are neuroactive steroids; that is, they affect
brain function, although they are not neurotransmitters in the
usual sense. Circulating steroids enter the brain with ease, and
neurons have numerous sex steroid and glucocorticoid recep-
tors. In addition to acting in the established fashion by bind-
ing to DNA (genomic effects), some steroids seem to act
rapidly by a direct effect on cell membranes (nongenomic
effects). The effects of steroids on GABA receptors have been
discussed previously. Evidence has now accumulated that the
brain can produce some hormonally active steroids from sim-
pler steroid precursors, and the term neurosteroids has been
coined to refer to these products. Progesterone facilitates the
formation of myelin, but the exact role of most steroids in the
regulation of brain function remains to be determined.
CHAPTER SUMMARY
■ Neurotransmitters and neuromodulators are divided into two
major categories: small-molecule transmitters (monoamines,
catecholamines, and amino acids) and large-molecule transmit-
ters (neuropeptides). Usually neuropeptides are colocalized
with one of the small-molecule neurotransmitters.
■ Monoamines include acetylcholine, serotonin, and histamine.
Catecholamines include norepinephrine, epinephrine, and do-
pamine. Amino acids include glutamate, GABA, and glycine.
■ Acetylcholine is found at the neuromuscular junction, in auto-
nomic ganglia, and in postganglionic parasympathetic nerve-
target organ junctions and some postganglionic sympathetic
nerve-target junctions. It is also found in the basal forebrain
complex and pontomesencephalic cholinergic complex. There
are two major types of cholinergic receptors: muscarinic (G pro-
tein-coupled receptors) and nicotinic (ligand-gated ion channel
receptors).
■ Serotonin (5-HT) is found within the brain stem in the midline
raphé nuclei which project to portions of the hypothalamus, the
limbic system, the neocortex, the cerebellum, and the spinal cord.
There are at least seven types of 5-HT receptors, and many of
these contain subtypes. Most are G protein-coupled receptors.
■ Norepinephrine-containing neurons are in the locus ceruleus
and other medullary and pontine nuclei. Some neurons also
contain PNMT, which catalyzes the conversion of norepineph-
rine to epinephrine. Epinephrine and norepinephrine act on α
and β receptors, with norepinephrine having a greater affinity
for α-adrenergic receptors and epinephrine for β-adrenergic re-
ceptors. They are G protein-coupled receptors, and each has
multiple forms.
■ The amino acid glutamate is the main excitatory transmitter in
the CNS. There are two major types of gluatamate receptors:metabotropic (G protein-coupled receptors) and ionotropic
(ligand-gated ion channels receptors, including kainite, AMPA,
and NMDA).
■ GABA is the major inhibitory mediator in the brain. Three sub-
types of GABA receptors have been identified: GABAA and
GABAC (ligand-gated ion channel) and GABAB (G protein-
coupled). The GABAA and GABAB receptors are widely distrib-
uted in the CNS.
■ There are three types of G protein-coupled opioid receptors (μ,
κ, and δ) that differ in physiological effects, distribution in the
brain and elsewhere, and affinity for various opioid peptides.MULTIPLE-CHOICE QUESTIONS
For all questions, select the single best answer unless otherwise directed.- Which of the following is a ligand-gated ion channel?
A) VIP receptor
B) norepinephrine receptor
C) GABAA receptor
D) GABAB receptor
E) metabotropic glutamate receptor - Which of the following synaptic transmitters is not a peptide,
polypeptide, or protein?
A) substance P
B) met-enkephalin
C)β-endorphin
D) serotonin
E) dynorphin - Activation of which of the following receptors would be
expected to decrease anxiety?
A) nicotinic cholinergic receptors
B) glutamate receptors
C) GABAA receptors
D) glucocorticoid receptors
E) α 1 -adrenergic receptors - Which of the following receptors is coupled to a heterotrimeric
G protein?
A) glycine receptor
B) GABAB receptor
C) nicotinic acetylcholine receptor at myoneural junction
D) 5-HT 3 receptor
E) ANP receptor - Which of the following would not be expected to enhance nor-
adrenergic transmission?
A) A drug that increases the entry of arginine into neurons.
B) A drug that enhances tyrosine hydroxylase activity.
C) A drug that enhances dopamine β-hydroxylase activity.
D) A drug that inhibits monoamine oxidase.
E) A drug that inhibits norepinephrine reuptake.
CHAPTER RESOURCES
Boron WF, Boulpaep EL: Medical Physiology. Elsevier, 2005.
Cooper JR, Bloom FE, Roth RH: The Biochemical Basis of
Neuropharmacology, 8th ed. Oxford University Press, 2002.
Fink KB, Göthert M: 5-HT receptor regulation of neurotransmitter
release. Pharmacol Rev 2007;59:360.