Autonomic nervous system norepinephrine

Dopamine, norepinephrine, and epinephrine (adrenalin) are biologically active amines that are collectively termed catecholamines. Dopamine and norepinephrine function as neurotransmitters in the brain and the autonomic nervous system. Norepinephrine and epinephrine are also synthesized in the adrenal medulla. 

Epinephrine is released from the adrenal medulla by activation of the sympathetic nerves of the autonomic nervous system. Norepinephrine is released from the adrenal medulla. About 20% of the total catecholamine released from the adrenal is norepinephrine. Most norepinephrine released by sympathetic nerves is taken back up into presyn-aptic neurons. A small amount diffuses into the blood and circulates throughout the body. When the sympathetic nervous system is highly activated, the amount of norepinephrine entering the circulation increases. 

Sympathetic nervous system. That portion of the autonomic nervous system that utilizes norepinephrine as a neurotransmitter at its neuroeffector junctions. 

Adrenal medulla. Derived from neural crest tissue, the adrenal medulla forms the inner portion of the adrenal gland. It is the site of production of the catecholamines, epinephrine and norepinephrine, which serve as a circulating counterpart to the sympathetic neurotransmitter, norepinephrine, released directly from sympathetic neurons to the tissues. As such, the adrenal medulla and its hormonal products play an important role in the activity of the sympathetic nervous system. This is fully discussed in Chapter 9, which deals with the autonomic nervous system. 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

Figure 14.1 Effect of autonomic nervous system stimulation on action potentials of the sinoatrial (SA) node. A normal action potential generated by the SA node under resting conditions is represented by the solid line the positive chronotropic effect (increased heart rate) of norepinephrine released from sympathetic nerve fibers is illustrated by the short dashed line and the negative chronotropic effect (decreased heart rate) of acetylcholine released from parasympathetic nerve fibers is illustrated by the long dashed line.

The autonomic nervous system is itself divided into two parts the sympathetic and parasympathetic nervous systems. The sympathetic nervous system serves several glands and involuntary muscles. The primary neurotransmitter of the sympathetic nervous system is norepinephrine, which acts through a and p adrenergic receptors. 

The physiological effects of the catecholamines are mediated by a large number of different receptors that are of particular interest in pharmacology. Norepinephrine acts in the autonomic nervous system and certain areas of the brain. Epinephrine is also used as a transmitter by some neurons. 

D. Acetylcholine and norepinephrine are important neurotransmitters in the peripheral autonomic nervous system but are not nearly as prominent in the CNS. Glycine is a major inhibitory neurotrans-... 

Ang II also interacts with the autonomic nervous system. It stimulates autonomic ganglia, increases the release of epinephrine and norepinephrine from the adrenal medulla, and—what is most important—facilitates sympathetic transmission by an action at adrenergic nerve terminals. The latter effect involves both increased release and reduced reuptake of norepinephrine. Ang II also has a less important direct positive inotropic action on the heart. 

Hess s model is all the more prescient because, at the time of its articulation, the cellular and molecular neurobiology of the central instantiation of the two branches of the autonomic nervous system were completely unknown. He had to infer their existence from his knowledge of the peripheral system and from the effects of his manipulation of the brain upon their outflow. The breakthrough came only in the early 1960s, when Anica Dahlstrom, K]ell Euxe, and others identified the norepinephrine containing cells of the locus coeruleus and the serotonin containing cells of the midline raphe nucleus. And it was even later when Marcel Mesulam and others mapped the central cholinergic neuronal system. 

FIGURE 18-2 Receptor classifications and subclassifications for acetylcholine (ACh] and norepinephrine [NE], the two primary neurotransmitters used in the autonomic nervous system. 

The release of epinephrine and norepinephrine from the adrenal medulla is controlled by the sympathetic division of the autonomic nervous system. As discussed in Chapter 18, sympathetic cholinergic preganglionic neurons directly innervate this gland. An increase in sympathetic activity causes increased firing in these neurons, which in turn stimulates the release of epinephrine and norepinephrine from the adrenal medulla. 

FIGURE 14.5 The autonomic nervous system innervates smooth muscle, cardiac muscles, and gland. ACh = acetylcholine N = nicotinic cholinergic receptors M = muscarinic cholinergic receptors S = sympathetic chain P = parasympathetic chain E = epinephrine D = dopamine NE = norepinephrine Sup. = superior Inf. = inferior. 

The brain and the immune system are accepted as the two major body s adaptive systems (Elenkov et al., 2000). The brain can modulate immune functions and the immune system also sends messages to the brain. The communication between these two systems is done mainly by the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). The sympathetic nervous system (SNS), which is part of the ANS, innervates the lymphoid organs (Elenkov et al., 2000) (Flierl et al., 2007). Catecholamines, like dopamine, serotonin, epinephrine and norepinephrine, are the end products of the SNS. 

Adrenergic transmission is well known to be involved in the regulation of homeostatic control through its functions in the autonomic nervous system. Additionally, adrenergic projections in the brain have been identified with important roles in neurocognition. Adrenoreceptors are seven transmembrane G-protein-coupled receptors that mediate the physiological responses of epinephrine and norepinephrine. The first classification of these receptors resolved a (alpha)-adrenoreceptors (aARs) from P (beta)-adrenoreceptors (PARs) (Ahlquist, 1948). Since then, additional subtypes and variants have been described. 

Q4 The ganglionic transmitter of both divisions of the autonomic nervous system is acetylcholine. The major postganglionic neurotransmitter of the sympathetic nervous system is norepinephrine (noradrenaline), but a small number of structures are innervated by sympathetic, cholinergic fibres. These fibres release acetylcholine and the structures innervated include the sweat glands and blood vessels supplying skeletal muscle. In the parasympathetic system the postganglionic neurotransmitter is acetylcholine. 

Norepinephrine Mostly excitatory, but inhibitory in some areas. Secreted by neurons in the locus ceruleus (subcortical area) to widespread areas of the brain, controlling wakefulness, overall activity, and mood. Also diffusely secreted in the sympathetic nervous system. Diffuse and widespread symptoms, including depression, changes in blood pressure, heart rate, and diffuse physiological responses, among many others. An important transmitter in the sympathetic branch of the autonomic nervous system. Diffusely affected by many medications. Several antidepressants work specifically on this neurotransmitter and its receptor sites. Many medications for general medical conditions affect this neurotransmitter as well. 

Noradrenergic model. This model suggests that the autonomic nervous system of anxious patients is hypersensitive and overreacts to various stimuli. The locus ceruleus may have a role in regulating anxiety, as it activates norepinephrine release and stimulates the sympathetic and parasympathetic nervous systems. Chronic noradrenergic overactivity down regulates 02-adrenoreceptors in patients with generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD). Patients with social anxiety disorder (SAD) appear to have a hyperresponsive adrenocortical response to psychological stress. 

Smooth muscle is unstriated with innervations from 2 both sympathetic (flight or fight) and parasympathetic (more relaxed) nerves of the autonomic nervous system. E. Smooth muscle appears unstriated under a polarized light microscope, because the myofilaments inside are less or-ganized. Smooth muscle fibers contain actin and myosin myofilaments which are more haphazardly arranged than they are in skeletal muscles. The sympathetic neurotransmitter, Ach, and parasympathetic neurotransmitter, norepinephrine, activate this type of muscle tissue. 

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