Catecholamines sources

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

Indicate the source, factors regulating the release, and physiological significance of the following vasoconstrictors catecholamines, angiotensin II, vasopressin, endothelin, and thromboxane A2... 

Catecholamines from non-neuronal intracellular and extracellular sources can interact with cells of the immune system. Recently, NE and EPI that can be released by activating stimuli have been detected in lymphocytes and macrophages [reviewed in 2], These cells may synthesize catecholamines and/or take up and store catecholamines from extracellular sources (i.e., NE released from sympathetic nerves or NE and EPI present in the plasma). 

Some of these environmental aspects are obvious, such as anthropogenic sources of chemicals that disrupt the structure of delicate epithelia involved in solute transport, or directly inhibit the solute transporting proteins (e.g. Cu inhibition of Na+K+ ATPase [82]). The general effects of environmental stress are also well known, since many of the hormones released into the blood during stressful situations will alter the activity of ion transporters (e.g. corticosteroids, catecholamine [14]). 

The adrenal glands are located anatomically above the kidneys. They comprise a three-layer cortex and a medulla. The medulla is the source of catecholamines such as epinephrine, the fight-or-flight hormone. The cortex is the source of aldosterone, the primary mineralocorticoid that is involved in the regulation of sodium reabsorption in the kidneys. In addition, the cortex is also the source of steroids known as glucocorticoids, of which cortisol is the principal endogenous representative. Synthesis and release of cortisol is under the control of adrenocorticotropic hormone (ACTH). 

Insulin is probably the most important inhibitor of lipolysis. In contrast to adults, in whom catecholamines represent the most important stimulators of lipolysis, thyrotropin (TSH) is the most important stimulator of lipolysis in the newborn. Plasma free fatty acid concentrations rise markedly in the first hours after birth in response to a marked increase in the TSH concentration and a fall in the insulin concentration. The fatty acids released from lipid stores are oxidized by some extrahepatic tissues (e.g., heart and skeletal muscle, kidney, intestine, and lung). Because the respiratory quotient (the ratio of carbon dioxide production to oxygen use) falls from a value of 1.0 (showing that carbohydrate oxidation is the primary source of energy) to a value of 0.8 to 0.9 (showing increasing oxidation of protein or fatty acids) at 2 to 12 hours of age, at a time when protein catabolism is usually insignificant, fatty acid oxidation must represent... 

The pulsed source (time-resolved) method then distinguishes between the emissions of several fluorescing species by using their decay-times rather than their fluorescence intensities. This means that several strongly overlapping fluorescences such as those of catecholamines can be quantitated simultaneously without chemical or mechanical separation. 

The mood and anxiety disorders in their various permutations constitute a major source of personal suffering and impaired ability to engage in productive Avork and interpersonal relationships. Between 5 and 9% of women and between 2 and 3% of men meet the diagnostic criteria for major depression at any time 10-25% of all women suffer major depression sometime in their lives, while 5-10% of men will develop major depressive disorder (American Psychiatric Association, 1994). The anxiety disorders obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, and generalized anxiety disorder (GAD) show lifetime prevalence rates of approximately 2.5%, 7%, 2.5%, and 5% respectively. Between 3 and 13% of individuals in community samples are regarded to meet the diagnostic criteria for social phobia. Mood and anxiety disorders are common comorbidities (American Psychiatric Association, 1994) and the most common antidepressant medications including the serotonin reuptake inhibitors, the mixed serotonin-catecholamine reuptake inhibitors, the tricyclic antidepressants, and the monoamine oxidase inhibitors, are all effective treatments for anxiety and panic attacks. 

Fig. 1. Effects of lack of glucagon ( ), catecholamine ( ), growth hormone (A), and cortisol (O) responses on counter-regulatory changes in glucose production (top) and glucose utilization (bottom) in non-diabetic volunteers. (Source Gerich, 1988.)...

Peripheral Dopaminergic System Dopamine is usually thought of as a neurotransmitter in the brain or as an intermediate in the production of norepinephrine and epinephrine in the periphery. It has been presumed tliat these sources account for the large amounts of dopamine and dopamine metabolites excreted in urine. The contribution of the brain to circulating levels and urinary excretion of dopamine metabolites is, however, now known to be relatively minor. Also, in sympathetic nerves and the adrenal medulla most dopamine is converted to norepinephrine. Therefore other sources and functions of dopamine in the periphery must be considered. Emerging evidence suggests the presence of a third peripheral catecholamine system, in which dopamine functions not as a neurotransmitter or circulating hormone, but as an autocrine or paracrine substance. ... 

Interpretation of a biochemical test result as normal or abnormal depends on availability of valid reference intervals (see Chapter 16). For tests of a single analyte, such as VMA, it can be expected that at least 2.5% of patients without pheochromocytomas will have values for the analyte above the upper reference limit and 2.5% below the lower reference limit. Up to a 5% incidence of false-positive results might be expected for tests of pairs of analytes, such as norepinephrine and epinephrine in tests of urinary or plasma catecholamines or normetanephrine and metanephrine in tests of plasma free or urinary fractionated metanephrines. False-positive rates usually, however, tend to be higher than expected this is likely due to reduced control over sampling conditions and sources of interference or differences in clinical characteristics of reference and patient populations. 

Vanillylmandehc Acid (VMAj is a major catecholamine metabolite formed by the actions of catechol-0-methyl-transferase and MAO. It is excreted by the kidney and represents an average of 40% to 50% of the urinary excretion production of norepinephrine and epinephrine. Norepinephrine is the major source of VMA, with metabolism through MHPG as the major pathway. VA4A is not significantly conjugated and therefore is measured without a hydrolysis step. VMA was first isolated and identified in the urine of a patient with a pheochromocytoma, and its analysis is commonly performed to detect the presence of pheochromocytomas and neuroblastomas. 

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