Porth's Essentials of Pathophysiology, 4e

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Nervous System

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Catecholamines and Adrenergic Receptors The catecholamines constitute a class of neurotransmit- ters and hormones that occupy key positions in the regu- lation of physiological processes and the development of neurological, psychiatric, endocrine, and cardiovascular diseases. Catecholamines are characterized by a catechol group (a benzene ring with two hydroxyl groups) to which is attached an amine (nitrogen-containing) group. Among the catecholamines are norepinephrine, epineph- rine, and dopamine. Norepinephrine is released at most sympathetic nerve endings. The adrenal medulla, which is a modified neural crest tissue, produces epinephrine along with small amounts of norepinephrine. Dopamine, which is an intermediate compound in the synthesis of norepinephrine, also acts as a neurotransmitter. It is the principal inhibitory transmitter of interconnecting neu- rons in the sympathetic ganglia. It also has vasodilator effects on renal, splanchnic, and coronary blood vessels when given intravenously and is sometimes used in the treatment of shock (see Chapter 20). All catecholamines are synthesized in the brain, the adrenal medulla, and by some sympathetic nerve fibers. Synthesis of dopamine and norepinephrine begins in the axoplasm of sympathetic nerve terminals from the amino acid tyrosine according to the following sequence: tyro sine → dopa → dopamine → norepinephrine (Fig. 34-24B). In the adrenal gland, an additional step takes place dur- ing which approximately 80% of the norepinephrine is transformed into epinephrine. Each of the steps in sympathetic neurotransmitter syn- thesis requires a different enzyme, and the type of neu- rotransmitter that is produced depends on the types of enzymes that are available in a nerve terminal. For exam- ple, the postganglionic sympathetic neurons that supply blood vessels have the needed enzymes for the synthesis of norepinephrine, whereas those in the adrenal medulla have the enzymes needed to convert norepinephrine into epinephrine. As the catecholamines are synthesized, they are stored in vesicles. The final step of norepinephrine synthesis occurs in these vesicles. When an action poten- tial reaches an axon terminal, the neurotransmitter mol- ecules are released from the storage vesicles. The storage vesicles provide a means for concentrated storage of the catecholamines and protect them from the cytoplasmic enzymes that degrade the neurotransmitters. In addition to neuronal synthesis, there is a second major mechanism for replenishment of norepinephrine in sympathetic nerve terminals. This mechanism consists of the active reuptake of the released neurotransmitter into the nerve terminal. Between 50% and 80% of the norepinephrine that is released during an action potential is removed from the synaptic area by an active reuptake process. This process terminates the action of the neu- rotransmitter and allows it to be reused by the neuron. The remainder of the released catecholamines diffuses into the surrounding tissue fluids or is degraded by two special enzymes: catechol- O -methyltransferase, which is diffusely present in all tissues, and monoamine oxidase (MAO), which is found in the nerve endings themselves. Catecholamines can cause excitation or inhibition of smooth muscle contraction, depending on the site, dose,

and type of receptor present. The excitatory or inhibitory responses of organs to sympathetic neurotransmitters are mediated by interaction with cell membrane receptors. There are two types of sympathetic receptors: α -adrenergic and β -adrenergic receptors. The α -adrenergic receptors have been further subdivided into α 1 and α 2 receptors, and β -adrenergic receptors into β 1 , β 2, and β 3 receptors. The α 1 receptors are primarily found in postsynaptic effector sites; they mediate responses in vascular smooth muscle. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal tract, kidney and brain. The α 2 receptors are mainly located presyn- aptically and can inhibit the release of norepinephrine from sympathetic nerve terminals. The α 2 receptors are abundant in the CNS and are thought to influence the central control of blood pressure. The β 1 receptors are primarily found in the heart; they mediate an increase in cardiac output by increasing heart rate (positive chrono- tropic effect), conduction velocity (positive dromotropic effect), and stroke volume (by enhancing contractility— positive inotropic effect). It can be selectively blocked by β 1 -receptor–blocking drugs, such as atenolol. The β 2 receptors are found in the bronchioles and in other sites, such as visceral smooth muscle of the GI tract, uterus, and urinary bladder. Actions of the β 2 receptor by smooth muscle relaxation facilitate respiration, inhibit GI tract motility, inhibit labor, and delay need of micturition. The β 3 receptor is located mainly in adipose tissue and is involved in the regulation of lipolysis and thermogenesis. ■■ The autonomic nervous system (ANS) functions at the subconscious level and is responsible for maintaining the visceral functions of the body.The two divisions of the ANS are the sympathetic and parasympathetic nervous systems. Although these divisions function in concert, they are generally viewed as having opposite and antagonistic actions.The sympathetic division maintains vital functions and responds when there is a critical threat to the integrity of the individual—the “fight- or-flight” response.The parasympathetic nervous system is concerned with conservation of energy, resource replenishment, and maintenance of organ function during periods of minimal activity. ■■ The outflow of both divisions of the ANS consists of a two-neuron efferent pathway: a preganglionic and a postganglionic neuron. Acetylcholine is the neurotransmitter for the preganglionic neurons for both ANS divisions, as well as the postganglionic neurons of the parasympathetic nervous system.The catecholamines, including dopamine, norepinephrine, and epinephrine, are the neurotransmitters for most sympathetic postganglionic neurons. SUMMARY CONCEPTS