Central and peripheral nervous systems

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Central and peripheral nervous systems

Key terms and definitions

Acetylcholine (ACH)

Chemical produced by the body that is used in the transmission of nerve impulses. It is destroyed by the enzyme cholinesterase.

Adrenergic (adrenomimetic)

Refers to a drug stimulating a receptor for norepinephrine or epinephrine.


Signals that are transmitted to the brain and spinal cord.


Refers to a drug blocking a receptor for norepinephrine or epinephrine.


Refers to a drug blocking a receptor for acetylcholine.

Central nervous system (CNS)

System that includes the brain and spinal cord, controlling voluntary and involuntary acts.

Cholinergic (cholinomimetic)

Refers to a drug causing stimulation of a receptor for acetylcholine.


Signals that are transmitted from the brain and spinal cord.


Naturally occurring catecholamine, produced by the adrenal medulla, that has properties similar to epinephrine. It is used as a neurotransmitter in most sympathetic terminal nerve sites.


Agent blocking or inhibiting the effects of the parasympathetic nervous system.


Agent causing stimulation of the parasympathetic nervous system.

Peripheral nervous system (PNS)

Portion of the nervous system outside the CNS, including sensory, sympathetic, and parasympathetic nerves.


Agent blocking or inhibiting the effect of the sympathetic nervous system.


Agent causing stimulation of the sympathetic nervous system.

The goal of Chapter 5 is to provide a clear introduction to and understanding of the peripheral nervous system; its control mechanisms, especially neurotransmitter functions; and its physiologic effects in the body. Understanding of the control mechanisms and physiologic effects forms the basis for a subsequent understanding of drug actions and drug effects, both for agonists and for antagonists that act at various points in the nervous system. This chapter concludes with a summary of autonomic and other neural control mechanisms and their effects in the pulmonary system.

Nervous system

There are two major control systems in the body: the nervous system and the endocrine system. Both systems of control can be manipulated by drug therapy, which either mimics or blocks the usual action of the control system, to produce or inhibit physiologic effects. The endocrine system is considered separately in Chapter 11, which discusses the corticosteroid class of drugs. The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS), both of which offer sites for drug action. The overall organization of the nervous system may be outlined as follows:

Figure 5-1 is a functional, but not anatomically accurate, diagram of the central and peripheral nervous systems. The sensory branch of the nervous system consists of afferent neurons from heat, light, pressure, and pain receptors in the periphery to the CNS. The somatic portion (or motor branch) of the nervous system is under voluntary, conscious control and innervates skeletal muscle for motor actions such as lifting, walking, or breathing. This portion of the nervous system is manipulated by neuromuscular blocking agents, to induce paralysis in surgical procedures or during mechanical ventilation. The autonomic nervous system is the involuntary, unconscious control mechanism of the body, sometimes said to control vegetative or visceral functions. For example, the autonomic nervous system regulates heart rate, pupillary dilation and contraction, glandular secretion such as salivation, and smooth muscle in blood vessels and the airway. The autonomic nervous system is divided into parasympathetic and sympathetic branches.

Autonomic branches

Neither motor nor sensory branch neurons have synapses outside of the spinal cord before reaching the muscle or sensory receptor site. The motor neuron extends without interruption from the CNS to the skeletal muscle, and its action is mediated by a neurotransmitter, acetylcholine (Ach). This is in contrast to the synapses occurring in the sympathetic and parasympathetic divisions of the autonomic system. The multiple synapses of the autonomic system offer potential sites for drug action, in addition to the terminal neuroeffector sites.

The parasympathetic branch arises from the craniosacral portions of the spinal cord and consists of two types of neurons—a preganglionic fiber leading from the vertebrae to the ganglionic synapse outside the cord and a postganglionic fiber from the ganglionic synapse to the gland or smooth muscle being innervated. The parasympathetic branch has good specificity, with the postganglionic fiber arising very near the effector site (e.g., a gland or smooth muscle). As a result, stimulation of a parasympathetic preganglionic neuron causes activity limited to individual effector sites, such as the heart or the eye. Figure 5-2 illustrates the portions of the spinal cord where the parasympathetic and sympathetic nerve fibers originate.

The sympathetic branch arises from the thoracolumbar portion of the spinal cord and consists of short preganglionic fibers and long postganglionic fibers. Sympathetic neurons from the spinal cord terminate in ganglia that lie on either side of the vertebral column. In the ganglia, or the ganglionic chain, the preganglionic fiber makes contact with postganglionic neurons. As a result, when one sympathetic preganglionic neuron is stimulated, the action passes to many or all of the postganglionic fibers. The effect of sympathetic activation is widened further because sympathetic fibers innervate the adrenal medulla and cause the release of epinephrine into the general circulation. Circulating epinephrine stimulates all receptors responding to norepinephrine, even if no sympathetic nerves are present. Where the parasympathetic system allows discrete control, the design of the sympathetic system causes a widespread reaction in the body.

Parasympathetic and sympathetic regulation

There are general differences between the parasympathetic and sympathetic branches of the autonomic nervous system, which can be contrasted. Parasympathetic control is essential to life and is considered a more discrete, finely regulated system than sympathetic control. Parasympathetic effects control the day-to-day bodily functions of digestion, bladder and rectal discharge, and basal secretion of bronchial mucus. Overstimulation of the parasympathetic branch would render the body incapable of violent action, resulting in what is termed the SLUD syndrome: salivation, lacrimation, urination, and defecation. These reactions are definitely counterproductive to fleeing or fighting!

By contrast, the sympathetic branch reacts as a general alarm system and does not exercise discrete controls. This is sometimes characterized as a “fight-or-flight” system: heart rate and blood pressure increase, blood flow shifts from the periphery to muscles and the heart, blood sugar increases, and bronchi dilate. The organism prepares for maximal physical exertion. The sympathetic branch is not essential to life; animal models with sympathectomy can survive but are unable to cope with violent stress.


Another general feature of the autonomic nervous system, including sympathetic and parasympathetic branches, is the mechanism of neurotransmitter control of nerve impulses. Nerve impulse propagation is electrical and chemical (electrochemical). A nerve impulse signal is carried along a nerve fiber by electrical action potentials, caused by ion exchanges (sodium, potassium). At gaps in the nerve fiber between neurons (synapses), the electrical transmission is replaced by a chemical neurotransmitter. This is the chemical transmission of the electrical impulse, which occurs at the ganglionic synapses and at the end of the nerve fiber, termed the neuroeffector site. Identification of the chemical transmitters dates back to Loewi’s experiments in 1921 and is fundamental to understanding autonomic drugs and their classifications. The usual neurotransmitters in the PNS, including the ganglionic synapses and terminal sites in the autonomic branches, are shown in Figure 5-1 (Ach and norepinephrine).

The neurotransmitter conducting the nerve impulse at skeletal muscle sites is Ach, and this site is referred to as the neuromuscular junction, or the myoneural junction. In the parasympathetic branch, the neurotransmitter is also Ach at both the ganglionic synapse and the terminal nerve site, referred to as the neuroeffector site. In the sympathetic branch, Ach is the neurotransmitter at the ganglionic synapse; however, norepinephrine is the neurotransmitter at the neuroeffector site. There are two exceptions to this pattern, both in the sympathetic branch. Sympathetic fibers to sweat glands release Ach instead of norepinephrine, and preganglionic sympathetic fibers directly innervate the adrenal medulla, where the neurotransmitter is Ach. Sympathetic fibers that have Ach at the neuroeffector sites are cholinergic (for Ach) sympathetic fibers. “Cholinergic sympathetic” would be an apparent contradictory combination of terms if not for the exceptions to the rule of norepinephrine as the sympathetic neurotransmitter. For example, sweating can be caused by giving a cholinergic drug such as pilocarpine, although this effect is under sympathetic control. “Breaking out in a sweat,” along with sweaty palms and increased heart rate resulting from circulating epinephrine, are common effects of stress or fright mediated by sympathetic discharge.

Although it is an oversimplification, an easy way to learn the various neurotransmitters initially is to remember that Ach is the neurotransmitter everywhere (skeletal muscle, all ganglionic synapses, and parasympathetic terminal nerve sites) except at sympathetic terminal nerve sites, where norepinephrine is the neurotransmitter. The exceptions provided by sympathetic fibers releasing Ach can be remembered as exceptions to the general rule.

Efferent and afferent nerve fibers

The autonomic system is generally considered an efferent system—that is, impulses in the sympathetic and parasympathetic branches travel from the brain and spinal cord out to the various neuroeffector sites, such as the heart, gastrointestinal tract, and lungs. Afferent nerves run alongside the sympathetic and parasympathetic efferent fibers and carry impulses from the periphery to the cord. The afferent fibers convey impulses resulting from visceral stimuli and can form a reflex arc of stimulus input–autonomic output analogous to the well-known somatic reflex arcs, such as the knee-jerk reflex. The mechanism of a vagal reflex arc mediating bronchoconstriction is discussed further in Chapter 7, in conjunction with drugs used to block the parasympathetic impulses.

Terminology of drugs affecting the nervous system

Terminology of drugs and drug effects on the nervous system can be confusing and may seem inconsistent. The confusion is due to the fact that drugs and drug effects are derived from the type of nerve fiber (parasympathetic or sympathetic) or, alternatively, the type of neurotransmitter and receptor (Ach and norepinephrine). The following terms are based on the anatomy of the nerve fibers, to describe stimulation or inhibition:

Additional terms are used, based on the type of neurotransmitter and receptor. Cholinergic refers to Ach, and adrenergic is derived from adrenaline, another term for epinephrine, which is similar to norepinephrine and can stimulate sympathetic neuroeffector sites. Because Ach is the neurotransmitter at more sites than just parasympathetic sites, and because receptors exist on smooth muscle or blood cells without any nerve fibers innervating them, these terms denote a wider range of sites than the anatomically based terms such as parasympathomimetic. Cholinergic can refer to a drug effect at a ganglion, a parasympathetic nerve ending site, or the neuromuscular junction. Adrenergic describes receptors on bronchial smooth muscle or on blood cells, where there are no sympathetic nerves. For this reason, cholinergic and adrenergic are not strictly synonymous with parasympathetic and sympathetic. Cholinergic (cholinomimetic) refers to a drug causing stimulation of a receptor for Ach. Anticholinergic refers to a drug blocking a receptor for Ach. Adrenergic (adrenomimetic) refers to a drug stimulating a receptor for norepinephrine or epinephrine. Antiadrenergic refers to a drug blocking a receptor for norepinephrine or epinephrine. Cholinoceptor is an alternative term for cholinergic receptor, and adrenoceptor is an alternative term for adrenergic receptor.

Parasympathetic branch

Cholinergic neurotransmitter function

In the parasympathetic branch, the neurotransmitter Ach conducts nerve transmission at the ganglionic site and at the parasympathetic effector site at the end of the postganglionic fiber. This action is illustrated in Figure 5-3. The term neurohormone has also been used in place of neurotransmitter. Ach is concentrated in the presynaptic neuron (both at the ganglion and at the effector site). Ach is synthesized from acetyl-CoA and choline, catalyzed by the enzyme choline acetyltransferase. Ach is stored in vesicles as quanta of 1000 to 50,000 molecules per vesicle. When a nerve impulse (action potential) reaches the presynaptic neuron site, an influx of calcium is triggered into the neuron. Increased calcium in the neuron causes cellular secretion of the Ach-containing vesicles from the end of the nerve fiber. After release, the Ach attaches to receptors on the postsynaptic membrane and initiates an effect in the tissue or organ site.

Ach is inactivated through hydrolysis by cholinesterase enzymes, which split the Ach molecule into choline and acetate, terminating stimulation of the postsynaptic membrane. In effect, the nerve impulse is “shut off.” There are also receptors on the presynaptic neuron, termed autoreceptors, that can be stimulated by Ach to regulate and inhibit further neurotransmitter release from the neuron. The effects of the parasympathetic branch of the autonomic system on various organs are listed in Table 5-1. Drugs can mimic or block the action of the neurotransmitter Ach, to stimulate parasympathetic nerve ending sites (parasympathomimetics) or to block the transmission of such impulses (parasympatholytics). Both categories of drugs affecting the parasympathetic branch are commonly seen clinically. The effects of the parasympathetic system on the heart, bronchial smooth muscle, and exocrine glands should be mentally reviewed before considering parasympathetic agonists or antagonists (blockers):


Effects of Parasympathetic Stimulation on Selected Organs or Sites

SA node Slowing of rate
Contractility Decreased atrial force
Conduction velocity Decreased AV node conduction
Smooth muscle Constriction
Mucous glands Increased secretion
Vascular Smooth Muscle  
Skin and mucosa No innervation*
Pulmonary No innervation*
Skeletal muscle No innervation
Coronary No innervation*
Salivary Glands Increased secretion
Skeletal Muscle None
Iris radial muscle None
Iris circular muscle Contraction (miosis)
Ciliary muscle Contraction for near vision
Gastrointestinal Tract Increased motility
Gastrointestinal Sphincters Relaxation
Urinary Bladder  
Detrusor Contraction
Trigone sphincter Relaxation
Skeletal muscle None
Sweat Glands None
Lipolysis (Multiple Sites) None
Renin Secretion (Kidney) None
Insulin Secretion (Pancreas) Increased

AV, Atrioventricular; SA, sinoatrial.

*No direct parasympathetic nerve innervation; response to exogenous cholinergic agonists is dilation.

Dilation occurs as a result of sympathetic cholinergic discharge or as a response to exogenous cholinergic agonists.

Sweat glands are under sympathetic control; receptors are cholinergic, however, and the response to exogenous cholinergic agonists is increased secretion.

Muscarinic and nicotinic receptors and effects

Two additional terms are used to refer to stimulation of receptor sites for Ach; they are derived from the action in the body of two substances, the alkaloids muscarine and nicotine. Receptor sites that are stimulated by these two chemicals are illustrated in Figure 5-4.

Muscarinic effects

Muscarine, a natural product from the mushroom Amanita muscaria, stimulates Ach (cholinergic) receptors at the parasympathetic terminal sites: exocrine glands (lacrimal, salivary, and bronchial mucous glands), cardiac muscle, and smooth muscle (gastrointestinal tract). Ach receptors at these sites and the effects of parasympathetic stimulation at these sites are termed muscarinic. A muscarinic effect well known to respiratory care clinicians is the increase in airway secretions after administration of Ach-like drugs such as neostigmine. There is also a decrease in blood pressure caused by slowing of the heart and vasodilation. In general, a parasympathomimetic effect is the same as a muscarinic effect, and a parasympatholytic effect is referred to as an antimuscarinic effect.

Subtypes of muscarinic receptors

Parasympathetic receptors and cholinergic receptors in general with or without corresponding nerve fibers are classified further into subtypes. These differences among cholinergic or muscarinic (M) receptors are based on different responses to different drugs, or recognition through use of DNA probes. Five muscarinic receptor subtypes have been identified: M1, M2, M3, M4, and M5. They are all G protein–linked (see Chapter 2). As G protein–linked receptors, these five subtypes of muscarinic receptors share a structural feature common to such receptors—a long, “serpentine” polypeptide chain that crosses the cell membrane seven times (illustrated for G protein receptors in Chapter 2). Table 5-2 summarizes the muscarinic receptor subtypes, with their predominant location and the type of G protein with which they are coupled. Additional details about muscarinic receptor location and function in the pulmonary system are presented in the final section of this chapter, which summarizes nervous control and receptors in the lung.


Muscarinic Receptor Subtypes, Location, and G-Protein Linkage

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M1 Parasympathetic ganglia, nasal submucosal glands Gq