Catecholamines sympathetic innervation

Madden, K.S., Catecholamines, sympathetic innervation, and immunity, Brain Behav. 

The third important feature distinguishing catecholamines from neu-ronally released norepinephrine involves epinephrine s affinity for -receptors. Norepinephrine has a very limited affinity for these receptors. Therefore, circulating epinephrine causes effects that differ from those of direct sympathetic innervation, including ... 

Sympathetic nerves are distributed to most vascular beds. They are most abundant in the renal, gastrointestinal, splenic, and cutaneous circulations. Recall that these tissues receive an abundant blood flow, more than is necessary simply to maintain metabolism. Therefore, when blood is needed by other parts of the body, such as working skeletal muscles, sympathetic vasoconstrictor activity reduces flow to the tissues receiving excess blood so that it may be redirected to the muscles. Interestingly, there is no sympathetic innervation to cerebral blood vessels. In fact, these vessels do not have a.j-adrenergic receptors, so they cannot be affected by circulating catecholamines. No physiological circumstance exists in which blood should be directed away from the brain. 

The action of catecholamines released at the synapse is modulated by diffusion and reuptake into presynaptic nerve terminals. Catecholamines diffuse from the site of release, interact with receptors and are transported back into the nerve terminal. Some of the catecholamine molecules may be catabolized by MAO and COMT. The cate-cholamine-reuptake process was originally described by Axelrod [18]. He observed that, when radioactive norepinephrine was injected intravenously, it accumulated in tissues in direct proportion to the density of the sympathetic innervation in the tissue. The amine taken up into the tissues was protected from catabolic degradation, and studies of the subcellular distribution of catecholamines showed that they were localized to synaptic vesicles. Ablation of the sympathetic input to organs abolished the ability of vesicles to accumulate and store radioactive norepinephrine. Subsequent studies demonstrated that this Na+- and Cl -dependent uptake process is a characteristic feature of catecholamine-containing neurons in both the periphery and the brain (Table 12-2). 

Adrenoceptors of the /3-subtype are important mediators of the sympathetic activation of the heart, kidney, and bronchi. /3-Adrenoceptors are also found in other organs and tissues such as blood vessels and the central nervous system. Accordingly, /3-adrenoceptor antagonists or jS-blockers inhibit the stimulating influence of the endogenous catecholamines (noradrenaline, adrenaline) on the various organs and tissues which are subject to sympathetic innervation. In cardiovascular medicine the /3-blockers are used in particular to blunt the sympathetic activation of the heart and kidneys. These effects are mediated by the /3i-subtype of the /3-adrenoceptors. The currently used /3-blockers are all competitive antagonists of the /3i-adrenoceptor, which is the basis of their therapeutic application. 

Human beings react with increased sympathoadrenal activity when they are confronted with challenging events or situations demanding active involvement The secretion in the peripheral blood of the catecholamines adrenaline and noradrenaline are important parts of this reaction. Sympathetic innervation via the splanchtuc nerve stimulates the adrenal medulla. This gland secretes adrenaline and a small fraction of the circulating noradrenaline in the blood. The latter hormone is secreted mainly at the ptesynaptic endplates of the (postganglionic) sympathetic nerve fibers. It has been shown that the ex-... 

Tyrosine hydroxylase and dopamine- -hydroxylase occur only in those cells which synthesize catecholamines (adrenal medullary cells and adrenergic neurons). When the sympathetic innervation of peripheral organs is destroyed (surgically, immunologically or chemically) these enzyme activities disappear. This is not true of DOPA decarboxylase, which occurs in many cells apart from those involved in catecholamine biosynthesis. This enzyme, for example, is also found in S-hydroxy-tryptamine-containing cells, and in the kidney, liver and certain glial cells associated with cerebral blood vessels. 

Although neuronal uptake appears to be the dominant inactivation process in tissues with a dense sympathetic innervation (Para. 5.2.8), this may not be true for all tissues. In some, such as the aorta, adrenergic fibres are only sparsely distributed, often at some distance from the effector cells. Here the enzymatic catabolism of catecholamines may play a more important rdle in inactivation. Similarly catabolism is an important factor in terminating the actions of circulating catecholamines, following their release from the adrenal medulla, or the injection of exogenous amines. 

The increased force of contraction induced by NA in the heart muscle is one of the consequences which follow when the sympathetic innervation to the heart is stimulated. This response is mediated by sympathetic receptors which are classified as of the j9 type, since the effects are more potently produced by iso-prenaline. and are antagonized by -antagonist drugs but not by a-antag(mist drugs. Biochemical studies of the effects of catecholamines on the isolated perfused heart have shown that the inotropic effect is accompanied by a large rise in the intracellular concentration of cyclic AMP in the cardiac cells. Furthermore, this rise occurs very rapidly after exposure to the catecholamine, and slightly precedes the recorded inotropic effect (Fig. 14). There is an excellent correlation between the... 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

Because catecholamines travel in the blood, organs and tissues throughout the body are exposed to them. Therefore, they are capable of stimulating tissues that are not directly innervated by sympathetic nerve fibers, hepato-cytes, and adipose tissue, in particular. As a result, the catecholamines have a much wider breadth of activity compared to norepinephrine released from sympathetic nerves. 

Similarly, under certain disease conditions, altered NA innervation and/or AR signaling capacity impairs sympathetic communication with cells of the immune system, influencing disease progression. Altered catecholamine communication with the immune system is evident in autoimmune diseases such as arthritis and multiple sclerosis [5-7] and in infectious diseases, such as leprosy and a mouse model of acquired immunodeficiency syndrome [15, 43, 44], The impact of altered NA innervation of... 

This group consists of j3-adrenergic receptor blockers, the antiarrhythmic activity of which is associated with inhibition of adrenergic innervation action of the circulatory adrenaline on the heart. Because all 8-adrenoblockers reduce stimulatory sympathetic nerve impulses of catecholamines on the heart, reduce transmembrane sodium ion transport, and reduce the speed of conduction of excitation, sinoatrial node and contractibility of the myocardium is reduced, and automatism of sinus nodes is suppressed and atrial and ventricular tachyarrhythmia is inhibited. 

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. 

The activation of the stress systems affects all tissues of the organism, and the peripheral immune system is no exception. These effects are mediated through at least tw o pathways via the HPA axis and by virtue of the innervation of lymphatic tissues by autonomic nerve fibers, especially from the sympathetic nervous system. All lymphoid tissues, primary (bone marrow and thymus) as well as secondary (spleen, lymph nodes, and gut-associated lymphoid tissue) are innervated by sympathetic nerve fibers. As discussed above, most lymphoid cells express catecholamine receptors, including B-lymphocytes, CD4- and CD 8-positive T cells, dendritic cells, monocytes, and macrophages. 

The answer is e. (Murray, pp 307-346. Scriver, pp 1667—1724. Sack, pp 121-138. Wilson, pp 287—3177) In humans, tyrosine can be formed by the hydroxylation of phenylalanine. This reaction is catalyzed by the enzyme phenylalanine hydroxylase. A deficiency of phenylalanine hydroxylase results in the disease called phenylketonuria [PKU(261600)]. In this disease it is usually the accumulation of phenylalanine and its metabolites rather than the lack of tyrosine that is the cause of the severe mental retardation ultimately seen. Once formed, tyrosine is the precursor of many important signal molecules. Catalyzed by tyrosine hydroxylase, tyrosine is hydroxylated to form L-dihydroxyphenylalanine (dopa), which in turn is decarboxylated to form dopamine in the presence of dopa decarboxylase. Then, norepinephrine and finally epinephrine are formed from dopamine. All of these are signal molecules to some degree. Dopa and inhibitors of dopa decarboxylase are used in the treatment of Parkinson s disease, a neurologic disorder. Norepinephrine is a transmitter at smooth-muscle junctions innervated by sympathetic nerve libers. Epinephrine and dopamine are catecholamine transmitters synthesized in sympathetic nerve terminals and in the adrenal gland. Tyrosine is also the precursor of thyroxine, the major thyroid hormone, and melanin, a skin pigment. 

It has been suggested that the vasodilation observed on stimulation of sympathetic fibers is a result of a sympathetic cholinergic innervation. In a recent study, Feigl stimulated the stellate ganglion and hypothalamus and found no evidence of cholinergic mediated coronary vasodilation. Information obtained by sympathetic stimulation of the coronary circulation has been recently criticized. The distribution of alpha and beta receptors within the coronary vasculature may vary with species and physiological state of the animal. Different experimental approaches may favor stimulation of either alpha or beta receptors. Other factors may be involved such as dose or time dependent actions of catecholamines on different receptors. 

The catecholamines epinephrine and norepinephrine (adrenaline and noradrenaline) originate in the inner medullar region of the adrenal glands. Stimulation of the adrenal by the sympathetic nervous system leads to secretion of catecholamines into the bloodstream. In addition, adipose tissue is itself directly innervated by the sympathetic nervous system. Various types of metabolic stress trigger the sympathetic nervous system to release its neurotransmitter, norepinephrine, directly into adipose where its effects on the adipocyte are mediated by specific plasma membrane adrenoreceptors. Rapid reflex responses are primarily stimulated by the sympathetic nervous system, whereas more long-term (i.e., on the scale of hours, days, and weeks) and/or basal effects are subject to regulation by catecholamine secretion. 

The adrenal medulla and other chromaffin tissue are embryologically and anatomically similar to sympathetic ganglia. The adrenal medulla differs from sympathetic ganglia in that its principal catecholamine is epinephrine (Epi, adrenaline), notNE. The chromaffin cells in the adrenal medulla are innervated by typical preganglionic fibers that release ACh. 

Several biogenic substances have been implicated as mediators in the induction of pulmonary vasoconstriction. Since the pulmonary vasculature is innervated by the sympathetic nervous system, it would appear that catecholamines released by the nerve endings are involved in neurogenic vasoconstriction. However there does seem to be a difference in the response of the pulmonary vasculature to endogenously released norepinephrine as compared with the response to that administered exogenously. 

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