Ganong's Review of Medical Physiology, 23rd Edition

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146 SECTION II Physiology of Nerve & Muscle Cells Other Substances Prostaglandins are derivatives of arachidonic acid found in the nervous system. They are present in nerve-ending fractions of brain homogenates and are released from neural tissue in vitro. A putative prostaglandin transporter with 12 membrane-spanning domains has been described. However, prostaglandins appear to exert their effects by modulating reactions mediated by cAMP rather than by functioning as synaptic 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 receptors. In addition to acting in the established fashion by binding 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 simpler 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 transmitters (neuropeptides). Usually neuropeptides are colocalized with one of the small-molecule neurotransmitters. ■ Monoamines include acetylcholine, serotonin, and histamine. Catecholamines include norepinephrine, epinephrine, and dopamine. Amino acids include glutamate, GABA, and glycine. ■ Acetylcholine is found at the neuromuscular junction, in autonomic ganglia, and in postganglionic parasympathetic nervetarget 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 protein-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 norepinephrine 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 receptors. 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 subtypes of GABA receptors have been identified: GABA A and GABA C (ligand-gated ion channel) and GABA B (G proteincoupled). The GABA A and GABA B receptors are widely distributed 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. 1. Which of the following is a ligand-gated ion channel? A) VIP receptor B) norepinephrine receptor C) GABA A receptor D) GABA B receptor E) metabotropic glutamate receptor 2. 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 3. Activation of which of the following receptors would be expected to decrease anxiety? A) nicotinic cholinergic receptors B) glutamate receptors C) GABA A receptors D) glucocorticoid receptors E) α 1 -adrenergic receptors 4. Which of the following receptors is coupled to a heterotrimeric G protein? A) glycine receptor B) GABA B receptor C) nicotinic acetylcholine receptor at myoneural junction D) 5-HT 3 receptor E) ANP receptor 5. Which of the following would not be expected to enhance noradrenergic 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.
Kandel ER, Schwartz JH, Jessell TM (editors): Principles of Neural Science, 4th ed. McGraw-Hill, 2000. Monaghan DT, Bridges RJ, Cotman CW: The excitatory amino acid receptors: Their classes, pharmacology, and distinct properties in the function of the central nervous system. Ann Rev Pharmacol Toxicol 1989;29:365. Nadeau SE, et al: Medical Neuroscience, Sauders, 2004. CHAPTER 7 Neurotransmitters & Neuromodulators 147 Olsen RW: The molecular mechanism of action of general anesthetics: Structural aspects of interactions with GABA A receptors. Toxicol Lett 1998;100:193. Owens DF, Kriegstein AR: Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 2002;3:715. Squire LR, et al (editors): Fundamental Neuroscience, 3rd ed. Academic Press, 2008.
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Copyright © 2010 by The McGraw-Hil
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iv Key Features of the 23rd Edition
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About the Authors KIM E. BARRETT Ki
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viii CONTENTS 27. Digestion, Absorp
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2 SECTION I Cellular & Molecular Ba
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10 SECTION I Cellular & Molecular B
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80 SECTION II Physiology of Nerve &
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196 SECTION III Central & Periphera
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302 SECTION IV Endocrine & Reproduc
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430 SECTION V Gastrointestinal Phys
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490 SECTION VI Cardiovascular Physi
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588 SECTION VII Respiratory Physiol
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640 SECTION VIII Renal Physiology T
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642 SECTION VIII Renal Physiology m
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644 SECTION VIII Renal Physiology F
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646 SECTION VIII Renal Physiology N
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650 SECTION VIII Renal Physiology G
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652 SECTION VIII Renal Physiology t
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654 SECTION VIII Renal Physiology I
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660 SECTION VIII Renal Physiology C
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662 SECTION VIII Renal Physiology d
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668 SECTION VIII Renal Physiology p
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670 SECTION VIII Renal Physiology l
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672 SECTION VIII Renal Physiology A
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676 SECTION VIII Renal Physiology E
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678 SECTION VIII Renal Physiology o
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680 SECTION VIII Renal Physiology I
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682 SECTION VIII Renal Physiology C
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688 Answers to Multiple Choice Ques
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690 INDEX Angiotensin III, 671 Angi
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692 INDEX Cannabinoids, 145, 179 Ca
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694 INDEX Climbing fibers, 255 Clin
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696 INDEX Endocrine functions of pa
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698 INDEX Flaccid paralysis, 244 Fl
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700 INDEX Hearing (continued) affer
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702 INDEX Intrinsic system, 532 Int
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704 INDEX Monoamines (continued) hi
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706 INDEX Pacemaker (continued) imp
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708 INDEX Proprioceptors, 632-633 P
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710 INDEX Respiratory compensation,
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712 INDEX Supratentorial lesions, 2
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714 INDEX Vestibular system, 213-21
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Ganong's Review of Medical Physiology, 23rd Edition

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