Plasma dopamine

Sowers J. R., Vlachakis N. (1984). Circadian variation in plasma dopamine levels in man. J. Endocrinol. Invest. 7(4), 341-5. 

Cubells, J.F., Kranzler, H.R., McCance-Katz, E., Anderson, G.M., Malison, R.T., Price, L.H., and Gelernter, J. (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5 56-63. 

Murphy DL, Donnelly C, Moskowitz J Inhibition by lithium of prostaglandin El and norepinephrine effects on cyclic adenosine monophosphate production in human platelets. Chn Pharmacol Ther 14 810-814, 1974b Murphy DL, Lake CR, et al Psychoactive drug effects on plasma norepinephrine and plasma dopamine B-hydroxylase in man, in Catecholamines Basic and Clinical Frontiers. Edited by Usdin E, Kopin IJ, Barchas J. Ehnsford, NY, Pergamon, 1979, pp 918-920... 

Dunnette J, Weinshilbourn RM (1977) Inheritance of low immunoreactive human plasma dopamine hydroxylase. Radioimmunoassay studies. J Clin Invest 609 1080... 

The major clinical feature of patients with deficiency of dopamine p-hydroxylase is orthostatic hypotension caused by reduced synthesis and release of norepinephrine by sympathetic nerves. The deficiency is characterized neuro-chemically by decreased levels of norepinephruie and norepinephrine metabolites and increased levels of dopamine and dopamine metabolites. Diagnosis is best achieved from an increased ratio of plasma dopamine to norepinephrine. Copper deficiency in Menkes disease is due to defects in the gene coding for a copper-transporting adenosine triphosphatase. Because dopamine p-hydroxylase is a copper-dependent enzyme, the deficiency is associated with decreased activity of the enzyme and reduced production of norepinephrine from dopamine. Prompt diagnosis at childbirth is essential for copper-replacement therapy, and... 

Goldstein DS, Swoboda KJ, Miles JM, Coppack SW, Aneman A, Holmes C, et al. Sources and physiological significance of plasma dopamine sulfate. J Clin Endocrinol Metab 1999 84 2523-31. 

Zabetian CP, Buxbaum SG, Elston RC, Kohnke MD, Anderson GM, Gelernter J, Cubells JF (2003) The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 72 1389-1400... 

Bhaduri N, Mukhopadhyay K (2008) Correlation of plasma dopamine beta-hydroxylase activity with polymorphisms in DBH gene a study on eastern Indian popu-laion. Cell Mol Neurobiol 28 343-350... 

An elevated plasma dopamine-j8-hydroxylase is associated in some cases of Lesch-Nyhan syndrome with the hypoxanthine guanine phosphoribosyl transferase activity. The hydroxylase is found, among other sites, in the synaptic vesicles where it converts dopamine to norepinephrine. Elevation of the hydroxylase occurs when the patients are exposed to stress that generates acute sympathetic stimulation. Blood pressure does not increase as it does in normal individuals. Those individuals with low transferase, but normal hydroxylase activity do not mutilate themselves. 

Plasma dopamine-) -hydroxylase Approximately 5% of the normal population have undetectable plasma D. The diagnosis of DpH deficiency, therefore, cannot be made solely on the basis of undetectable plasma DpH, On the other hand its presence rules out the diagnosis. 

If CSF is not available, highly elevated plasma and urine levels of 30MD point to AADC deficiency. More modest elevations are found in deficiency. Measurement of plasma dopamine and norepinephrine will distinguish between these two conditions. 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Noradrenaline transporters (NAT) are localized in the presynaptic plasma membrane of adrenergic nerve terminals. They belong to a family of proteins with 12 putative transmembrane proteins which are responsible for recycling of released neurotransmitters (noradrena-line/adrenaline, dopamine, serotonin, amino acid transmitters) back into the presynaptic nerve ending. Noradrenaline transporters can be blocked by a number of different antidepressant drags, including tricyclic antidepressants (e.g. desipramine) and selective noradrenaline reuptake inhibitors (e.g. reboxetine). 

The vesicular monoamine transporters (VMATs) were identified in a screen for genes that confer resistance to the parkinsonian neurotoxin MPP+ [2]. The resistance apparently results from sequestration of the toxin inside vesicles, away from its primary site of action in mitochondria. In addition to recognizing MPP+, the transporter s mediate the uptake of dopamine, ser otonin, epinephrine, and norepinephrine by neurons and endocrine cells. Structurally, the VMATs show no relationship to plasma membrane monoamine transporters. 

These drugs are thought to prolong the effect of levodopa by blocking an enzyme, catechol-O-methyltransferase (COMT), which eliminates dopamine. When given with levodopa, the COMT inhibitors increase the plasma concentrations and duration of action of levodopa... 

Those for the D2 receptor (e.g. bromocriptine) have a particular value in the treatment of Parkinson s disease by reproducing the effects of the dopamine lost through degeneration of the nigrostriatal tract (Chapter 15). They are also used to reduce the undesirable effects of prolactinaemia (high plasma prolactin), such as amenorrhoea and galactorrhoea. 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

Levodopa, a dopamine precursor, is the most effective agent for PD. Patients experience a 40% to 50% improvement in motor function. It is absorbed in the small intestine and peaks in the plasma in 30 to 120 minutes. A stomach with excess acid, food, or anticholinergic medications will delay gastric emptying time and decrease the amount of levodopa absorbed. Antacids decrease stomach acidity and improve levodopa absorption. Levodopa requires active transport by a large, neutral amino acid transporter protein from the small intestine into the plasma and from the plasma across the blood-brain barrier into the brain (Fig. 29-2). Levodopa competes with other amino acids, such as those contained in food, for this transport mechanism. Thus, in advanced disease, adjusting the timing of protein-rich meals in relationship to levodopa doses may be helpful. Levodopa also binds to iron supplements and administration of these should be spaced by at least 2 hours from the levodopa dose.1,8,16,25... 

Following the release of dopamine, the primary mode of removal from the synapse is reuptake into the presynaptic neuron via the dopamine transporter (DAT). DAT is dependent upon the energy created by the Na+/K+ pump and is a member of the Na+/Cl -dependent plasma membrane transporter family, as are the norepinephrine and 7-aminobutyric acid (GABA) transporters. Imaging studies utilizing compounds with highly specific affinity for DAT... 

Some less obvious phenomena of catecholamine transport and biosynthesis further illustrate the complexities of deciphering how efferents from midbrain dopamine neurons contribute to sleep-wake regulation. The plasma membrane norepinephrine transporter (NET), which is responsible for the uptake of extracellular noradrenaline, can also readily transport dopamine, and does so in vivo. This... 

Hagan M. M., Havel P. J., Seeley R. J. et al (1999). Cerebrospinal fluid and plasma leptin measurements covariability with dopamine and cortisol in fasting humans. J. Clin. Endocrinol. Metah. 84(10), 3579-85. 

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