Catecholamines substances

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The phenylalkylamine hallucinogens show a close structural resemblance to the catecholamines, noradrenahne and dopamine. The prototype structure is found in mescaline, a naturally occurring substance. Modification of the mescaline molecule has led to synthetic amphetamine derivatives with hallucinogenic action. 

The detection limits for catecholamines are 10 to 50 ng substance per chromatogram zone [11] and 50 ng substance per chromatogram zone for carbaryl and a series of other... 

Because duration of activity of the catecholamines is significantly longer than that of neuronally released norepinephrine, the effects on tissues are more prolonged. This difference has to do with the mechanism of inactivation of these substances. Norepinephrine is immediately removed from the neuroeffector synapse by way of reuptake into the postganglionic neuron. This rapid removal limits duration of the effect of this neurotransmitter. In... 

The most commonplace substrates in energy-transfer analytical CL methods are aryl oxalates such as to(2,4,6-trichlorophenyl) oxalate (TCPO) and z s(2,4-dinitrophenyl) oxalate (DNPO), which are oxidized with hydrogen peroxide [7, 8], In this process, which is known as the peroxyoxalate-CL (PO-CL) reaction, the fluorophore analyte is a native or derivatized fluorescent organic substance such as a polynuclear aromatic hydrocarbon, dansylamino acid, carboxylic acid, phenothiazine, or catecholamines, for example. The mechanism of the reaction between aryl oxalates and hydrogen peroxide is believed to generate dioxetane-l,2-dione, which may itself decompose to yield an excited-state species. Its interaction with a suitable fluorophore results in energy transfer to the fluorophore, and the subsequent emission can be exploited to develop analytical CL-based determinations. 

Several additional useful publications demonstrating practical applications of CE/MS methods for neurotransmitter analysis and neuropharmaceutical studies are those of Larsson and Lutz (2000) (neuropeptides including substance P) Hettiarachchi et al. (2001) (synthetic opioid peptides) Varesio et al. (2002) (amyloid-beta peptide) Zamfir and Peter-Katalinic (2004) (gangliosides) Peterson et al. (2002) (catecholamines and metanephrines) Cherkaoui and Veuthey (2002) (fluoxetine) and Smyth and Brooks (2004) (various lower molecular weight molecules including benzodiazepines, steroids, and cannabinols). 

Tornkvist A, Sjoberg PJ, Markides KE, Bergquist J. 2004. Analysis of catecholamines and related substances using porous graphite carbon as separation media in liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 801 323. 

The rate-limiting step in the synthesis of the catecholamines from tyrosine is tyrosine hydroxylase, so that any drug or substance which can reduce the activity of this enzyme, for example by reducing the concentration of the tetrahydropteridine cofactor, will reduce the rate of synthesis of the catecholamines. Under normal conditions tyrosine hydroxylase is maximally active, which implies that the rate of synthesis of the catecholamines is not in any way dependent on the dietary precursor tyrosine. Catecholamine synthesis may be reduced by end product inhibition. This is a process whereby catecholamine present in the synaptic cleft, for example as a result of excessive nerve stimulation, will reduce the affinity of the pteridine cofactor for tyrosine hydroxylase and thereby reduce synthesis of the transmitter. The experimental drug alpha-methyl-para-tyrosine inhibits the rate-limiting step by acting as a false substrate for the enzyme, the net result being a reduction in the catecholamine concentrations in both the central and peripheral nervous systems. 

Several amino acids are broken down by de-carbo qflation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.l2) and of pantetheine (see pp. 108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p.356). The transmitter dopamine is also a precursor for the catecholamines epinephrine and norepinephrine (see p.352). The biogenic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan. 

Pharmacology Vitamin C, a water-soluble vitamin, is an essential vitamin in man however, its exact biological functions are not fully understood. It is essential for the formation and the maintenance of intercellular ground substance and collagen, for catecholamine biosynthesis, for synthesis of carnitine and steroids, for conversion of folic acid to folinic acid and for tyrosine metabolism. 

The adrenomimetic drugs can be divided into two major groups on the basis of their chemical structure the catecholamines and the noncatecholamines. The catecholamines include norepinephrine, epinephrine, and dopamine, all of which are naturally occurring, and several synthetic substances, the most important of which is isoproterenol (isopropyl norepinephrine). The skele-... 

The presence of a-methyldopa and its metabolites in the urine reduces the diagnostic value of urinary catecholamine measurements as an indicator of pheochro-mocytoma, since these substances interfere with the fluorescence assay for catecholamines. 

Substance Psychological effects in man Effects on behavior in animals Effects on catecholamines at brain synapses... 

In some cases, although no irreversible inactivation of an enzyme occurs, the action of a toxin may deprive an organism of a vital substance and recovery has to await resynthesis of this substance. Such is the case with reserpine, which acts by depleting sympathetic nerve endings of catecholamine the time required to replenish the reserves of catecholamine is longer than the persistence of reserpine in the tissue. 

---