Review of Medical Physiology - William F. Ganong 2002

Functions of the Nervous System
Autonomic Nervous System
Responses of Effector Organs to Impulses Arriving via Autonomic Nerves

Main Principles

Responses of visceral Organs to The stimulation of noradrenergic and cholinergic postganglionic nerve fibers are summarized in Table 13-2. The smooth Muscle in the walls of hollow visceral organs is generally innervated by both noradrenergic and cholinergic fibers; activation of one system typically increases smooth muscle activity, whereas activation of the other decreases it. However, there is no universal rule stating that a specific system invariably stimulates or inhibits an effector organ. In sphincter Muscles, for example, both adrenergic and cholinergic systems exert excitatory effects, with one system innervating the constrictor element and the other the dilator.

Acetylcholine is virtually absent from circulating Blood, and local cholinergic effects are predominantly discrete and short-lived due to the high concentration of the enzyme acetylcholinesterase in cholinergic nerve endings. Norepinephrine Functions as both a hormone and a neurotransmitter, exhibiting a more prolonged action than acetylcholine. Norepinephrine, epinephrine, and dopamine are all present in plasma (see Chapter 20). Epinephrine and dopamine are released by The adrenal medulla, whereas the majority of norepinephrine diffuses into the bloodstream directly from noradrenergic nerve endings. Metabolites of norepinephrine and dopamine also enter the Circulation from sympathetic nerve endings and smooth muscle Cells (Fig. 13-3). Catecholamine METABOLISM is detailed in Chapter 4. Notably, even when MAO and COMT are inhibited, The rate of norepinephrine metabolism remains high; however, the inhibition of its reuptake prolongs its half-life.

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Fig. 13-3. Metabolism of catecholamines in the sympathetic Nervous system. TH, Tyrosine hydroxylase; DOPA, dihydroxyphenylalanine; DA, dopamine; NE, norepinephrine; NMN, normetanephrine; DHPG, dihydroxyphenylglycol; HVA, homovanillic acid; MHPG, 3-methoxy-4-hydroxyphenylglycol; COMT, catechol-O-methyltransferase; DOPAC, dihydroxyphenylacetic acid. For other Abbreviations, see Figs. 4-18 and 4-20 (from DS Goldstein).

Cholinergic Influences

In general, the functions mediated by the cholinergic division of the Autonomic nervous system are related to the vegetative demands of daily life. For instance, cholinergic stimulation promotes Digestion and nutrient absorption by enhancing gastrointestinal motility, increasing gastric secretion, and relaxing the pyloric sphincter. Given this profile—and in contrast to the catabolic effects of the noradrenergic division—the cholinergic autonomic division is sometimes referred to as the anabolic nervous system.

The precise function of VIP (vasoactive intestinal peptide), which is co-released by postganglionic cholinergic Neurons, remains unclear, though it likely facilitates the postsynaptic actions of acetylcholine. Furthermore, because VIP is a vasodilator, it may also enhance blood flow to the target organs.

Noradrenergic Influences

The effects of the noradrenergic division become apparent during critical situations. They are particularly vital in preparing an individual to cope with extreme stress, although one must avoid the teleological fallacy of assuming the system acts deliberately to create such circumstances. For example, noradrenergic stimulation causes pupil dilation (allowing more light to enter the eye), accelerates Heart rate, elevates blood pressure (ensuring better perfusion of vital organs and skeletal muscles), and constricts cutaneous Blood Vessels (thereby minimizing blood loss from wounds). Noradrenergic activity also lowers activation thresholds in the reticular formation (enhancing alertness and arousal) while increasing blood levels of glucose and free Fatty acids to supply abundant energy. Consequently, Cannon termed this emergency noradrenergic system the "fight-or-flight" preparation response.

Beyond mediating mass responses during stress, noradrenergic autonomic fibers subserve numerous baseline functions as well. For example, tonic noradrenergic input to arterioles maintains blood pressure, and adjustments in this tone form the feedback mechanism—mediated via carotid sinus receptors—that regulates arterial pressure. Sympathetic activity decreases in starved animals and increases upon refeeding, which accounts for the reductions in blood pressure and metabolic rate observed during fasting and the corresponding increases following food consumption.

Small dense-core vesicles in postganglionic adrenergic neurons contain ATP and norepinephrine, whereas large dense-core vesicles contain neuropeptide Y. Evidence suggests that low-frequency stimulation preferentially releases ATP, whereas high-frequency stimulation promotes the release of neuropeptide Y. Nonetheless, the precise Functional Significance of ATP and neuropeptide Y co-release remains to be fully elucidated.

Table 13-3. Selected Pharmacological Agents and Toxins Affecting the Autonomic Nervous System¹

¹ Only primary effects are listed.

² Guanethidine is believed to have two major Mechanisms of action.

³ Clonidine stimulates peripheral a₂ receptors, but in addition, along with other a₂ agonists that cross the blood-Brain barrier, it stimulates central a₂ receptors in the brain, thereby dampening autonomic outflow.

Pharmacology of the Autonomic Nervous System

The synaptic junctions of the peripheral autonomic motor pathways serve as sites for the pharmacological modulation of visceral functions. This is logical, as transmission across these synapses is mediated by chemical transmitters. Neurotransmitters are synthesized, stored in nerve terminals, and released to act on neurons, muscle cells, or glandular cells. Receptor binding initiates the specific functions of these effector cells, after which the chemical transmitters are cleared via cellular uptake or metabolized. Each of these steps can be pharmacologically stimulated or inhibited, producing predictable physiological consequences. In noradrenergic nerve terminals, certain drugs induce the synthesis of compounds that displace norepinephrine within storage vesicles; these weak or inactive "false neurotransmitters" are subsequently released in place of norepinephrine when an Action Potential reaches the nerve terminal.

Selected pharmacological agents and toxins that affect autonomic synapses, along with their mechanisms of action, are presented in Table 13-3. Compounds with muscarinic-like activity include substances structurally related to acetylcholine as well as agents that inhibit acetylcholinesterase. Examples of the latter include the insecticide parathion and diisopropyl fluorophosphate (DFP), a component of so-called nerve gases that cause lethality through massive inhibition of acetylcholinesterase.